Download BACOFUN_2016 Meeting Booklet - Barrel Cortex Function 2016

Barrel Cortex Function
Amsterdam 2016
"a multidisciplinary, international meeting on
sensory (sub)cortical circuits"
Barrel Cortex Function Amsterdam 2016
19th of May, Day 1
Version 23rd April 2016
08:45 – 09:15 Registration, Coffee and Poster mounting
09:15 – 09:30 Welcome & Opening (Christiaan de Kock)
Session 1: “Development”, Chair Fritjof Helmchen
09:30 – 10:15 Gordon Fishell (Keynote)
“The integration of interneurons into brain circuits: a conversation
involving pedigree and communications”
10:15 – 10:45 Heiko Luhmann
“Role of spontaneous activity in early cortical development”
10:45 – 11.15 Coffee break & posters
Session 2: “Inhibition”, Chair Jochen Staiger
11:15 – 12:00 Adam Kepecs (Keynote)
“Behavioral role and impact of a VIP-mediated interneuron circuit”
12:00 – 12:30 Carl Petersen
“Neocortical cell-type-specific sensorimotor processing during goal-directed
behavior”
12:30 – 13:00 Koen Vervaeke
“Shining light on neural inhibition in the somatosensory cortex during
tactile sensation”
13.00 – 14:15 Lunch (restaurant section F, top floor)
Session 3: “Linking circuits to behavior”, Chair Christiaan de Kock
14:15 – 15:00 Anthony Holtmaat
“Mechanism for functional and structural plasticity”
15:00 – 15:30 Cornelius Schwarz
“Linking the barrel column. What is the functional basis of learned
associations?”
15:30 – 16.00 Fritjof Helmchen
“Neural correlates of tactile discrimination based on whisker touch”
16:00 – 16:15 Junior 1: Naoya Takahashi (Larkum lab)
“Dendritic dynamics in sensory perception”
16:15 – 16:30 Junior 2: Christian Ebbesen (Brecht lab)
“Vibrissa motor cortex activity suppresses contralateral whisker
movement”
16:30 – 17:00 Coffee break & posters
Session 4: – “From sparse to dense connectomics”, Chair Randy Bruno
17:00 – 17:45 Moritz Helmstaedter (Keynote)
“High-resolution connectomics”
17:45 – 18:15 Dirk Feldmeyer
“Excitatory and inhibitory connections in the barrel cortex - new vistas”
18:15 – 18:45 Marcel Oberlaender
“Cortical Drive by Deep Layer Networks”
18:45 – 19:00 Junior 3: Nora Jamann (Engelhardt lab)
“Plasticity of the axon initial segment in the mouse barrel cortex
19:00 – 19:15 Junior 4: Zeinab Fazlali (Arabzadeh lab)
“Correlation between Cortical State and Locus Coeruleus Activity:
Implications for Sensory Coding in Rat Barrel Cortex”
PLENARY BARBEQUE
(to join, advance registration for both meeting and BBQ is mandatory)
Barrel Cortex Function Amsterdam 2016
20th of May, Day 2
Session 5: “Cortical processing and behavior”, chair Dirk Feldmeyer
09:00 – 09:45 Michael Stryker (Keynote)
“A neural circuit that regulates cortical responsiveness and plasticity.”
09:45 – 10:15 James Poulet
“Sensorimotor transformation in the mouse forepaw system"
10:15 – 10:45 Michael Brecht
“Sex, Touch & Tickle”
10:45 – 11:15 Coffee break & Posters
Session 6: “Active somatosensation”, chair Heiko Luhmann
11:15 – 12.00 David Kleinfeld (Keynote)
“Cortical-trigeminal loops in the control of vibrissa movement”
12.00 – 12:30 Christiaan de Kock
“Cortical representation of naïve active touch”
12:30 – 13:00 Randy Bruno
“The many layers of neocortex”
13:00 – 14:00 Lunch (restaurant section F, top floor)
Session 7: chair Marcel Oberlaender
14:00 – 14:15 Junior 5: Hemanth Mohan (de Kock lab)
“Encoding of free whisking and object touch in the posterior
parietal cortex of rodents”
14:15 – 14:30 Junior 6: Teresa Guillamon Vivancos (Jennifer Luebke lab)
“Contribution of Distinct Progenitor Lineages to Neuronal Diversity
in Layer 4 of the Mouse Barrel Cortex”
14:30 – 14:45 Junior 7: Alexander van der Bourg (Helmchen lab)
“Laminar and columnar refinement of sensory coding in developing
mouse barrel cortex”
14:45 – 15.00 Junior 8: Guanxiao Qi (Feldmeyer lab)
“Inter-columnar synaptic transmission in thalamo-recipient layers
4 and 6A of rat barrel cortex”
15:00 – 15:15 Short break (no catering)
Session 8: “Inhibition-Disinhibition-Excitation”, chair Michael Brecht
15:15 – 16:00 Josh Huang (Keynote)
“Genetic dissection of cortical circuits: chandeliers light up
pyramids“
16:00 – 16:30 Miguel Maravall
“Exploring tactile temporal integration and sequence discrimination.”
16:30 – 17:00 Jochen Staiger
“The ins and outs of cortical VIP neurons”
17:00 concluding remarks (Christiaan de Kock)
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A.J . E R NSTSTRAAT
UILE NSTE DE
AMST E LVE E N
Barrel Cortex Function 2016, 19-20th of May 2016
SAP: 2961107
Tafel, hoog
Oranje/witte stoel
Tafel, laag
Posterbord
Buffettafel
Tafel, stevig
Klapstoel
180x80
Our meeting is supported by generous contributions from:
Barrel Cortex Function 2016, 19-20th of May 2016
Oranje/witte stoel
SAP: 2961107
Tafel, hoog
Posterbord
Klapstoel
Tafel, laag
Buffettafel
180x80
Tafel, stevig
Posters
Posters are available throughout the full meeting. The presenting author is
requested to be at the poster during the indicated time window.
Presenting author (lab)
Day 1: regular font
Day 2: bold
Presenting time
#1: Roel de Haan (de Kock)
#2: Berat Sermet (Petersen)
#3: Angeliki Vavladeli (Petersen)
#4: Pierre Le Merre (Crochet)
#5: Mike Guest (Oberlaender)
#6: Mythreya Seetharama (Oberlaender)
#7: Rajeevan Narayanan (Oberlaender)
#8: Daniel Udvary (Oberlaender)
#9: Jiali Tang (Feldmeyer)
#10: Claudia Barz (Feldmeyer)
#11: Vishalini Sivarajan (Feldmeyer)
#12: Francois Pauzin (Krieger)
#13: Guanxiao Qi (Feldmeyer)
#14: Manuel Marx (Feldmeyer)
#15: Matías Goldin (Shulz)
#16: Alexander van der Bourg (Helmchen)
#17: Lianne Klaver (Bosman)
#18: Stéphanie Miceli (Schubert)
#19: Teresa Guillamon-Vivancos (Luebke)
#20: Georg Hafner (Staiger)
#21: Keti Cohen-Kashi (Lampl)
#22: Ana Parabucki (Lampl)
#23: Desire Humanes-Valera (Krieger)
#24: Christian Ebbesen (Brecht)
#25: Mostafa Nashaat (Larkum)
#26: Jorrit Montijn (Pennartz)
#27: Anton Sumser (Groh)
#28: Zeinab Fazlali (Arabzadeh)
#29: Konrad Juczewski (Krieger, Hardingham)
Day 1, 16:30 – 17:00
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Poster #1
Probing the neurophysiological correlates of cognitive performance in
rat medial prefrontal cortex
Roel de Haan, Sven van der Burg, Anton Pieneman, Vinod Nigade, Huib
Mansvelder, Bert Sakmann, Christiaan de Kock
Attention, working memory and executive functions are strongly associated
with activity in rat medial prefrontal cortex (mPFC). Similar to other cortical
areas, the mPFC has a laminar architecture containing functionally different
cell types and layers. However, the contribution of individual layers and celltypes in mPFC to cognitive behavior is only beginning to be understood. To
reveal which components of the mPFC circuitry orchestrate the diverse
repertoire of prefrontal functions, we recorded populations of neurons at
specific cortical depths across layers of the rat mPFC during a whisker-based
go/no-go task.
In short, rats were trained to determine the location of a pole on the radius of
the whisker, where the proximal location should be reported by licking to
receive a water reward and in the distal location the rat should not lick to
avoid a 5 second time-out. We find populations of neurons with correlates to
most phases of the task. The strongest neurophysiological correlate involved
reward consumption after the rat made a correct decision. Further, we find
strong sub-threshold activity in the LFP when the rat is cued for the next trialstart, which could reflect a ‘reset’ of the working memory to prepare for
upcoming task execution.
Poster #2
Layer-specific thalamocortical input onto excitatory neurons in mouse
primary somatosensory barrel cortex
Berat Semihcan Sermet, Carl C. H. Petersen
In the mouse whisker system, sensory information is relayed to the primary
somatosensory barrel cortex by two major thalamic nuclei, the ventral
posterior medial nucleus (VPM) and the posterior medial nucleus (POM).
While the axonal innervation pattern of these two nuclei has been studied
anatomically in some detail, their synaptic input to distinct cell-types across
different layers in barrel cortex is incompletely understood. We used the
specificity of optogenetics to selectively stimulate axons from VPM or POM,
and we measured the evoked excitatory postsynaptic potentials in vitro with
whole-cell patch-clamp recordings. VPM or POM was infected in vivo with an
adenoassociated virus encoding the light-gated cation channel
channelrhodopsin (ChR2). Synaptic input onto individual neurons of the barrel
cortex was recorded in brain slices in vitro by activating the ChR2-expressing
thalamic axons with blue light. We measured thalamic inputs onto excitatory
neurons across all layers of the barrel cortex, finding that the biggest inputs
appeared to largely colocalise with the anatomical innervation pattern.
Anatomically, VPM preferentially innervates L4, deep L3 and the L5B/6A
border, and, functionally, we found that the biggest input was observed in L4,
followed by L2/3. Anatomically, POM innervates L5A and L1, and,
functionally, we found the biggest input in L5A, followed by L2/3. The onset
latencies were shortest in L4 and L5A for VPM and POM input respectively.
Our results begin to provide a more complete understanding of the distribution
of thalamic input onto excitatory neurons across the layers of the mouse
barrel cortex.
Poster #3
Two-photon calcium imaging of neocortical projection neurons in
mouse whisker primary somatosensory cortex during goal-directed
sensorimotor learning
Angeliki Vavladeli, Carl Petersen
How goal-directed sensorimotor learning induces changes in neuronal
networks to alter the flow of information between cortical areas is not well
understood. Here, using genetically-encoded calcium indicators in
combination with retrograde tracers and two-photon laser scanning
microscopy, we have begun to chronically image the activity of layer 2/3
neurons in primary somatosensory cortex (S1) that project to secondary
somatosensory cortex (S2p) or primary motor cortex (M1p), while mice learn a
simple goal-directed sensorimotor transformation. Thirsty mice were trained to
lick for water reward in response to single-whisker deflections and auditory
stimulation. We are analyzing how sensory input (whisker and auditory
stimuli) and motor output (licking and whisking) are represented by projection
neurons in S1 of mice performing the detection task and how their activity
evolves during the learning process.
Poster #4
Large-scale sensory integration in the mouse cortex during a tactile
detection task.
Pierre Le Merre, Paul Salin, Carl Petersen and Sylvain Crochet
Sensory perception leading to goal-directed behavior involves multiple,
spatially-distributed cortical areas. It has been hypothesized that sensory
information flows from primary sensory areas encoding mainly the properties
of the stimulus, to higher-order, more frontal areas encoding the valence of
the stimulus. To understand further the integration of sensory signals, we
have recorded sensory evoked potentials (SEPs) simultaneously from
different cortical areas, either in mice performing a whisker-based sensory
detection task (DT) or in mice exposed to same whisker stimulus that was not
associated with reward (Neutral Exposition, NE). In mice performing the DT,
we observed SEPs in response to the whisker stimulus in all recorded areas
with latencies increasing from the whisker primary somatosensory area (wS1)
to the secondary somatosensory area (wS2), the whisker motor area (wM1),
the parietal area (PtA), the dorsal hippocampus (dCA1) and the medial
prefrontal cortex (mPFC). We found a reduction of SEPs during Miss trials
compared to Hit trials in all areas except wS1, with strongest reduction in
mPFC and dCA1. We also observed a selective increase of the SEPs in
mPFC and dCA1 when the mice were trained to the DT but not during NE,
suggesting that DT training induced plastic changes in the mPFC and
hippocampus leading to increased SEPs in response to the conditioning
stimulus. Our results support the idea that mPFC and dCA1 could signal the
relevance of a sensory stimulus in the context of a well-defined behavior,
whereas sensory areas would be more constrained by the nature of the
stimulus.
Poster #5
Structural Basis for Sensory-Motor Whisker Control
Mike Guest, Elizabeth Wendel, Peter Strick, Marcel Oberlaender
The rodent vibrissal system offers an ideal model for studying sensory-motor
pathways in the mammalian central nervous system. There has been much
consideration to bring insight to the organization of the whisker sensory
pathways throughout the rodent brain. However, it is poorly understood how
brain-wide whisker motor pathways are organized and how, together with
sensory pathways, they constitute a sensory-motor loop that can provide
sensory feedback to the whiskers during tactile-based behaviors. It has been
previously reported that whisker muscles are directly innervated by vibrissal
motor neurons(vMN) located in the lateral area of the Facial Nucleus(FN) and
that these vMNs are directly innervated by output neurons of the vibrissal
motor cortex (Herfst and Brecht, 2007). It has also been suggested that this
vibrissal motor area of the cortex is divided into two segregated regions. 1) A
sensory input area called the Transitional Zone (TZ) and 2) a whisker motor
output area called vM1 (Smith & Alloway, 2013; Matyas et al., 2010).
In this study we inject wild type rabies virus into the mystacial pad targeting a
single muscle that is wrapped around a whisker follicle. The virus is
transported retrogradely across multiple synapses throughout the central
nervous system in a time dependent manner (Kelly and Strick, 2000), first
labeling vMNs located in the FN and subsequently the hierarchy of pathways
that provide input to these motor neurons. Combining this injection method
with custom-designed brain-wide imaging techniques and automated somata
detection software (Oberlaender et al., 2009), we provide unprecedented
quantitative insight to the organization of the whisker motor pathways, setting
the stage to investigate how cortex provides sensory feedback to peripheral
receptor organs during sensory-motor tasks.
Poster #6
Automated Detection of Putative Synaptic Contacts between in vivo
Labelled Neurons
Mythreya Seetharama, David Slabik, Alison Smyth, Marcel Oberlaender
Understanding the structural organization of the neural networks requires
reconstruction of the underlying neural circuitry in anatomical detail and
mapping of the synaptic contacts. A typical in vivo labeled axon innervates a
large volume and imaging such in vivo labeled pairs of neurons at high
resolution yields a large set of images, typically in the order of Tera Bytes.
Manual mapping of synaptic contacts between such cell pairs would be labor
intensive and error prone. Here, we present a software pipeline that
automatically detects putative synaptic contacts between the boutons and
spines of in vivo labeled pairs of neurons. The pipeline has three phases.
Firstly, the regions where the skeletons of axon and dendrites of different
neurons come close to each other are detected. Secondly, in these proximity
regions, the boutons along the axons and spines along the dendrites are
detected. Thirdly, the overlaps between boutons and spines along with their
locations are detected. The resulting putative contacts are visualized on the
original image stack using a visualization tool and can be verified by the user.
This semi-automated approach reduces the number of sites to be manually
inspected for putative contacts from tens of thousands to tens of putative
contact sites. Hence achieving about three orders of magnitude reduction in
the manual effort required.
Poster #7
Organizational principles of rat vibrissal motor cortex, an in vivo study
Rajeevan T Narayanan and Marcel Oberlaender
Vibrissal somatosensory cortex (vS1) and vibrissal motor cortex (vM1) are the
two key structures involved in somatosensation in rodents. Although we know
the vertical and horizontal organizational principles of vS1, very little is known
about the organizational principles of vM1 at single cell level. Using in vivo cell
attached recording, biocytin filling and semi-automatic reconstruction pipeline;
we investigated electrophysiological properties and morphological
characteristics of motor cortex neurons. We found substantial similarities
between these two areas, indicating that both cortices follow similar
organizational principles.
Poster #8
Dense Statistical Connectome of Rat Barrel Cortex
Daniel Udvary, Robert Egger, Vincent J. Dercksen, and Marcel Oberlaender
Synaptic connectivity is one important constrain for cortical signal flow and
function. Consequently, a complete synaptic connectivity map (i.e.,
connectome) of a cortical area across spatial scales would advance our
understanding of cortex organization and function. We present a dense
statistical connectome of the entire rat vibrissal cortex based on measured 3D
distributions of axons/dendrites/somata of excitatory and inhibitory neurons.
By calculating the structural overlap between pre- and postsynaptic cells our
model provides quantitative estimates on connectivity measurements like
connection probability and number of synapses on cell type, cellular, and
subcellular levels. We found that our model reproduces connectivity
measurements between thalamic and excitatory/inhibitory neurons reported in
paired recordings and light- and electron-microscopic studies. Similarly,
intracortical synaptic connectivity of our model matches most connectivity
measurements. However, the location and distance between pre- and
postsynaptic cells and - in case of slicing experiments - the degree of
truncation strongly influences the connectivity. When reproducing electronmicroscopic and in vitro slicing experiments in our model, we found that
measurements obtained under the respective experimental conditions are in
line with our model's results, but represent only a small fraction of the
underlying distribution. The experimental conditions such as the small volume
analyzed in electron-microscopic studies or the truncation of morphologies
thus biases the conclusions that are drawn, e.g. an underestimation of the
connection probability. Our approach can therefore be used to improve
experimental design and seen as a starting point to simulate sensory-evoked
signal flow and investigate structural and functional organization of the cortex.
Poster #9
Effects of Noradrenaline on Neuronal Networks in Rat Neocortex
Jiali Tang, Gabriele Radnikow, Dirk Feldmeyer
Previous studies on the effects of noradrenaline (NA) in the neocortex have
demonstrated its pivotal role in the regulation of brain function. Here, patch
clamp recordings from single and synaptically coupled neurons were used to
investigate the effects of NA on neocortical neuronal microcircuits. In
neocortical layer 4 (L4), NA induces a hyperpolarization of spiny neurons by
activation of inwardly rectifying K+ channels via α2 adrenoceptors, but
enhances the action potential firing rate by blocking hyperpolarizationactivated and cyclic nucleotide-gated (HCN) channels via α2 adrenoceptors in
response to suprathreshold stimuli. Furthermore, NA decreases synaptic
efficacy in L4 excitatory microcircuits by suppressing presynaptic
neurotransmitters release via activation of presynaptic α2 adrenoceptors.
Moreover, NA modulates the excitability of excitatory neurons in the neocortex
in a layer- and cell-type specific way: NA hyperpolarizes neurons in layers 4
and 5A, and depolarizes neurons in L5B and L6A. For L2/3 pyramidal
neurons, NA hyperpolarizes neurons with broad apical dendritic tufts, but
depolarizes those with slender apical dendritic tuft.
In addition, NA causes a depolarization of both fast-spiking and non fastspiking interneurons, thereby increasing the inhibitory tone and thus an overall
suppression of L4 excitatory microcircuit activity.
Here we have demonstrated that NA affects signal processing in the
neocortex via several different mechanisms, including a bi-directionally
regulation on the excitability of single excitatory neurons, the layer and celltype specific modulation of excitatory neurons throughout cortical layers, and
a homogenous facilitation of all interneuron types.
Poster #10
Functional and structural characteristics of layer 2/3 neurons in adult
mouse barrel cortex
Barz C. S., Feldmeyer D.
The accessibility for paired and multiple recordings and drug application make
the barrel cortex slice a popular system for studying neuronal and circuit
properties. For technical reasons, however, slice studies have mostly been
performed in young rats and mice (typically up to 3 weeks of age). In contrast,
neuronal properties in adult barrel cortex (> 6 weeks) have not been
described comprehensively so far. In particular, detailed knowledge about the
morphological and electrophysiological features of inhibitory neurons is
lacking. The present study characterizes the structure and function of layer
2/3 excitatory and inhibitory neurons in adult mouse barrel cortex. Whole-cell
patch clamp recordings with simultaneous biocytin fillings were performed in
thalamocortical brain slices obtained from C57BL/6J mice aged 6-21 weeks.
Post-hoc histological processing and 3D morphological reconstructions were
carried out for detailed analyses of dendritic and axonal processes. Based on
the morphological and electrophysiological cell properties, different
subclasses of excitatory and inhibitory neurons were identified. The results
provide an important basis for understanding the barrel cortex microcircuitry in
adult mice, as well as changes during long-term skill learning and alterations
in developmental disease models.
Poster #11
Characterization of non-fast spiking interneurons in layer 4 of rat barrel
cortex
Vishalini Sivarajan, Guanxiao Qi, Dirk Feldmeyer
GABAergic interneurons (INs) play an important role in providing balanced
cortical excitation, synchronized activity, and maintaining neuronal oscillatory
networks. Abnormalities of these functions have been associated with several
neurological and psychiatric disorders. Despite the low population of
GABAergic interneurons (10-20%), they display a vast heterogeneity in their
structure, function and neurochemical markers expression. Quantitative
classification of GABAergic interneurons based on reliable and stable criteria
is crucial to understand the different subtypes and their functions. In this
study, we investigated the different subtypes of non-fast spiking (nFS) INs and
their functional properties in layer 4 (L4) of rat barrel cortex using whole-cell
patch-clamp recordings, and morphological 3D reconstructions. We
performed quantitative morphological classification based on the positioning
and orientation of axonal projection patterns through different layers and
columns. We identified several distinct morphological subtypes of nFS
interneurons, in particular, lateral projecting interneurons. This kind of
projection pattern from one barrel to neighboring barrels is a novel finding,
and we believe that this kind of interneurons could play an important role in
lateral inhibition. Paired recordings of nFS L4 INs with other neuron types
showed that nFS INs establish weak synaptic connections with a low release
probability and small amplitude; the connections showed paired-pulse
facilitation. This is markedly different from the fast spiking interneurons, which
form strong synaptic connections that exhibit invariably paired-pulse
depression. Our findings reveal that nFS INs are elements of the L4 microcircuitry that exhibit very distinct connectivity patterns and functional roles in
the neuronal network.
Poster #12
Bi-phasic modulation of cortical excitability
Francois Pauzin, Veronika Gondzik, Desire Humanes-Valera, Patrik Krieger
Tactile sensory information is processed in the primary somatosensory cortex,
a structure organized in six different horizontal neuronal layers that are
interconnected to each other by vertical axonal projections. Each of them can
influence the response to sensory stimuli, but the specific role played by each
layer in cortical processing is still not fully understood. Here we show using
optogenetical tools that layer 6 in the primary somatosensory cortex of the
mouse plays a crucial role in controlling the gain of whisker evoked activity in
neurons of all cortical layers. This gain modulation results from the
coordinated action of layer 6 projections to inhibitory neurons whose cell body
resides in deep cortical layers and subcortical projections to the thalamus, the
main gateway for tactile information to reach the cerebral cortex. This study
thus establishes L6 as a major mediator of cortical gain modulation,
enlightening the role of cortico-cortical and cortico-thalamic feedback in
sensory processing.
Poster #13
Inter-columnar synaptic transmission in thalamo-recipient layers 4 and
6A of rat barrel cortex
Guanxiao Qi and Dirk Feldmeyer
In the primary somatosensory (barrel) cortex of rodents, layer 4 (L4) and (to a
lesser degree) L6A are the main thalamorecipient layers. Within a barrel
column excitatory and inhibitory neurons form local recurrent synaptic
microcircuits. However, little is known about synaptic connections between
cortical columns. The purpose of this study is a functional and structural
characterization of monosynaptic connections be-tween L4 or L6A neurons
located in two neighboring columns.
Monosynaptic connections (n=24) between L4 neurons located in two
neighboring barrels were obtained; the average inter-soma distance of preand postsynaptic neurons was 146 ± 46 µm. Of these L4 ‘intercolumnar’
connections 12 were excitatory-excitatory and 10 excitatory-inhibitory. The
pre- and postsynaptic excitatory neurons were either spiny stellate cells
(SSCs) or start pyramidal neurons. The postsynaptic inhibitory neurons were
predominantly fast-spiking (FS) interneurons. In addition, two monosynaptic
inhibitory connections from FS interneurons in one barrel to SSCs in the other
barrel were recorded.
Recordings from synaptically coupled L6A pyramidal neurons located in two
neighboring columns were also obtained.; the average inter-soma distance of
which was 226 ± 27 µm (n=5). For L6A excitatory connections, the
presynaptic neurons were exclusively cortico-cortical (CC) cells and
postsynaptic neurons are either CC cells or cortico-thalamic cells.
Our data show that there is direct inter-columnar signaling via monosynaptic
excitatory or inhibitory connections in both thalamorecipient layers 4 and 6A,
which is like to play an important role in shaping receptive field properties of
barrel cortical neurons.
Poster #14
Expression pattern and distribution of the forkhead-box protein P2
(FoxP2) in layer 6 of the somatosensory rat barrel cortex
Manuel Marx, Werner Hucko and Dirk Feldmeyer
In rodents, the transcription factor forkhead-box protein P2 (FoxP2) is highly
and exclusively expressed in neocortical layer 6. However, little information
about FoxP2 on the cellular level is available so far. Here, we examined layer
6A and layer 6B (L6A, L6B) neurons using whole-cell patch clamp single and
paired recordings. In addition, neurons were simultaneously filled with biocytin
and a fluorescent dye to allow a correlated analysis of FoxP2 expression
using antibody labeling and neuronal morphology. FoxP2 is consistently
expressed from late subplate stages (postnatal days P0-4) into adulthood
(>P35). We did not find any age-dependent changes in the FoxP2 cell count.
FoxP2 was only expressed in glutamatergic L6A and L6B neurons. All
GABAergic L6A and L6B interneurons were found to be FoxP2(-). The
expression of FoxP2 was also found to depend on the type of excitatory L6
neuron. In layer 6A, corticocortical (CC) pyramidal neurons were consistently
FoxP2(-) while corticothalamic (CT) pyramidal neurons were FoxP2(+). In
layer 6B, non-pyramidal excitatory neurons (i.e. multipolar, tangential,
horizontal and inverted neurons) were generally FoxP2(-). In contrast, all L6B
pyramidal neurons showed a clear FoxP2 expression, i.e. FoxP2(+). We
identified three L6-L6 connection types between FoxP2(+)-FoxP2(+),
FoxP2(+)-FoxP2(-) and FoxP2(-)-FoxP2(-) neurons. Moreover, FoxP2 is
highly expressed in subcortical regions like the striatum and in thalamic
nuclei. We hypothesize that FoxP2 is involved in corticocortical,
corticothalamic and corticostriatal microcircuits and may play a key role in
motor coordination.
Poster #15
Neural representation of multiwhisker tactile information in the
secondary somatosensory cortex
Matías A. Goldin*, Evan R. Harrell*, Daniel E. Shulz
* contributed equally
Tactile object discrimination in rodents is mediated by the vibrissal system
and its related processing areas in the brain. Efficient discrimination relies on
spatiotemporally correlated whisker deflections that provide the raw
information that animals use to make inferences about an object.
Here we studied the neuronal coding of these spatiotemporal correlations by
applying complex, multi-vibrissal stimuli in a controlled fashion using a matrix
of piezo-electric benders applied to the 24 caudal macrovibrissae of
isoflurane-anesthetized rats [Jacob et al. 2010]. This stimulator has already
facilitated a detailed characterization of the coding of inter-whisker correlation
in the primary somatosensory cortex (SI) [Estebanez et al. 2012], and here we
aim to extend this description to the secondary somatosensory cortex (SII).
We recorded activity of multiple single units with up to 64 channel multi-site
extracellular electrodes. Using a forward correlation approach, we found both
single and multiwhisker receptive fields, which tended to be more elongated
along whisker rows. We determined the response latencies and found that
they are compatible with SII being driven directly by thalamic inputs.
Our working hypothesis is that SII has a strong representation of large-scale,
multi-whisker patterns of stimulation, since vibrissal somatotopy in SII is much
less defined than in SI. This feature was studied with a reverse correlation
approach providing white noise stimuli in a fully correlated (all identical) or
uncorrelated (all different) fashion across 24 macrovibrissae. Preliminary
results show that global inter-whisker correlation has a relatively stronger
representation in SII than in SI.
Poster #16
Laminar and columnar refinement of sensory coding in developing
mouse barrel cortex
Alexander van der Bourg, Jenq-Wei Yang, Vicente Reyes-Puerta, Balazs
Laurenczy, Martin Wieckhorst, Maik C. Stüttgen, Heiko J. Luhmann and Fritjof
Helmchen
Rodent rhythmic whisking behavior matures during a critical period two weeks
after birth. The related adaptations of neocortical function remain poorly
understood. Here, we characterized neuronal dynamics in mouse barrel
cortex evoked by various spatiotemporal whisker stimulation patterns across
all cortical layers before, during and after the onset of whisking behavior. By
employing multi-electrode recordings and two-photon calcium imaging in
anesthetized mice, we found layer-specific changes in stimulus-evoked
activity from postnatal day P10 to P28, which decreases in layer 2/3 (L2/3)
and L4 neurons but increases in L5 and L6. During the same time period,
neuronal activity progressively spread further between neighboring barrel
columns, especially for superficial layers. Repetitive stimulation of multiple
whiskers showed distinct response profiles in the stimulated barrel columns
depending on the direction and temporal separation of the stimuli. Calcium
imaging of individual L2/3 neurons revealed that, in addition to progressive
sparsification and decorrelation of neuronal activity, response selectivity to
axial vs. lateral whisker movement emerged around the critical period. Our
results demonstrate a layer-specific refinement of sensory responses to
spatially and temporally distinct stimuli in developing mouse barrel cortex at
the onset of exploratory behavior.
Poster #17
Anatomical implications for multisensory areas in ferret cortex
Lianne Klaver, Chaira Serrarens, Umberto Olcese, Cyriel Pennartz & Conrado
Bosman
Multisensory integration (MI) refers to the combination of information from
multiple senses to produce coherent perceptual experiences. Classically, MI
has been studied in subcortical areas, yet little is known about the anatomical
organization underlying MI responses in neocortex. To study multisensory
integration in the cortex, we use domestic ferrets (Mustela putorius furo),
which are presumed to have a large capacity available for specialized
integration areas, due to cortical expansion.
Previously identified integration areas in cats include the antero- and
posteromedial lateral suprasylvian visual areas (AMLS and PMLS), located in
the multisensory zone between the primary auditory and visual cortices.
Furthermore, it has been shown in ferrets that multisensory areas are present
outside these multisensory zones, for example in the anterior ectosylvian
visual area (AEV) and in primary and secondary auditory areas of the ferret.
Nevertheless, an accurate description of putative integration areas in
multisensory zones is still missing.
Here, we aimed to provide an anatomical overview of the connectivity
between unisensory and multisensory integrative areas. We used BDA
(biotinylated dextran amine), an anterograde tracer, to determine overlapping
projections from primary auditory and visual cortices.
We confirmed the presence of projections from primary visual and auditory
cortex to AEV, primary and secondary unisensory areas. Furthermore,
preliminary results reveal previously unidentified projections from primary
visual and auditory cortex to several multisensory zones located between
these unisensory areas in the ferret. We believe that these results will be
relevant for a wide audience studying auditory, visual and audiovisual
processing in the ferret.
Poster #18
Reduced feedforward inhibition within layer IV of the barrel cortex and
altered sensory performance in serotonin transporter knockout rats.
Stéphanie Miceli, Nael Nadif Kasri, Joep Joosten, Chao Huang, Lara Kepser,
Rémi Proville, Martijn Selten, Fenneke van Eijs, Alireza Azarfar, Judith R.
Homberg, Tansu Celikel, and Dirk Schubert
High extracellular serotonin (5-HT) levels during development alter input into
the primary somatosensory cortex (S1) of rodents by impairing neural
transmission between the thalamus and cortical input layer IV (LIV). As one
consequence rodent models of impaired 5-HT transporter (SERT) function
show a disruption in their topological organization of the somatosensory
system both on thalamocortical and intracortical level. Here we investigate in
SERT-/- rats how elevated 5-HT affects the feed forward inhibition circuits,
which control afferent sensory information in LIV of S1. We show that an
increased exposure to 5-HT during early cortical development affects the
function of inhibitory networks within S1 by resulting in fewer functional somatargeting inhibitory synapses and a depolarized GABA reversal potential in S1
LIV. On the neural population level stimulation of LIV networks resulted in
increased excitatory responses in the intracortical circuits. Consequently, we
show that reduced efficiency of the feedforward inhibition circuit and
increased excitability along the LIV to LII/III pathway may underlie an
accelerated and more efficient sensory performance during tactile behavior.
Our results imply that serotonergic signaling during development affects
activity driven cortical network maturation and the processing of sensory
information.
Poster #19
Contribution of Distinct Progenitor Lineages to Neuronal Diversity in
Layer 4 of the Mouse Barrel Cortex
Teresa Guillamon-Vivancos, Maria Medalla, William Tyler, Tarik Haydar and
Jennifer Luebke
The striking diversity of neurons in the mammalian neocortex is key for the
specification of cortical areas, but how this diversity is achieved during
development is still poorly understood. Radial Glial Cells (RGCs), the neural
stem cells of the developing cortex, also generate intermediate progenitor
cells (IPCs), which in turn are able to generate new neurons. Our overall
hypothesis is that distinct IPCs are responsible for generation of neuronal
diversity in the neocortex. Our group recently showed that neurons derived
from different IPCs have distinct morphological and electrophysiological
properties in layers 2/3 of the mouse frontal cortex.
In this study we aimed to determine whether different IPCs contribute to
neuronal diversity in layer 4 of the barrel cortex, where several morphological
and physiological types of neurons have been described. Using a novel
genetic fatemapping technique we were able to simultaneously label
progenitors that express Tbr2 and progenitors that don’t in different colors, as
well as the neurons that derive from them. Through in utero electroporation at
embryonic day E13.5 we labeled neurons in layer 4 of the barrel cortex. We
studied whether neurons derived from distinct IPCs distributed differently
across the depth and the distinct compartments of the barrel field. We also
used whole-cell patch clamp recordings to assess the electrophysiological
properties of these neurons. During the recordings, neurons were filled and
their morphology studied using high-resolution confocal microscopy. This
study contributes to a better understanding of how different streams of
neurogenesis contribute to adult neuronal diversity and cortical organization.
Poster #20
The afferent connectome of VIP expressing GABAergic interneurons in
the mouse barrel cortex
Georg Hafner, Robin J. Wagener, Julien Guy, Mirko Witte, Martin K.
Schwarz, Karl-Klaus Conzelmann and Jochen F. Staiger
The very diverse population of inhibitory interneurons plays a fundamental
role in shaping cortical activity. Vasoactive intestinal polypeptide (VIP)
expressing interneurons have received attention as major integrators of longrange input into the local cortical network. However, from which areas they
receive projections has not been studied systematically. We visualized the
brain-wide monosynaptic afferent inputs to VIP interneurons in the mouse
barrel cortex using retrograde rabies virus tracing. This technique specifically
labels presynaptic cells with enhanced green fluorescent protein. More than
90% of cells presynaptic to VIP neurons were found locally within the barrel
cortex. Other reliably labeled cortical areas included ipsilateral primary
somatosensory (outside the whisker representation) and secondary
somatosensory, visual, auditory, motor and cingulate cortex as well as
contralateral barrel cortex. Subcortical projections originated from several
thalamic nuclei and the basal forebrain. In addition, we characterized the
neurochemistry of presynaptic inputs within the barrel cortex. Using in-situ
hybridization and immunohistochemistry, about 20% of inputs were
characterized as inhibitory and subclassified into somatostatin and
parvalbumin positive cells. In conclusion, our anatomical data suggest that
VIP neurons are mostly driven by local excitatory inputs but have the capacity
to integrate long-range inputs.
Poster #21
Local and thalamic origins of ongoing and sensory evoked cortical
correlations.
Keti Cohen-Kashi, Boaz Mohar, Akiva N. Rappaport and Ilan Lampl
The contribution of local circuits versus remote inputs in the generation of
synchronized activity in sensory cortices is poorly understood. In sensory
cortices, ascending information from the thalamus targets cells in L4.
However, the impact of these inputs is controversial. The majority of the
synaptic contacts in L4 are between neighboring cortical cells. Yet,
electrophysiological studies have suggested that thalamic inputs are powerful
enough to evoke the observed subthreshold response of L4 cells, without
requiring inputs from neighboring cortical cells. How then such a low number
of thalamic inputs can have such a profound impact on cortical response? A
widely accepted mechanism that explains the robust activation of L4 cells is
thalamic synchrony, implying that thalamic inputs of neighboring L4 cells are
highly correlated.
To investigate the role of both inputs in generation of cortical synchronization
we isolated the thalamic excitatory inputs of cortical cells by optogenetically
silencing cortical firing. In anesthetized mice we measured the correlation
between isolated thalamic synaptic inputs of simultaneously patched nearby
L4 cells of the barrel cortex. In contrast to correlated activity of excitatory
synaptic inputs in the intact cortex, isolated thalamic inputs exhibit
asynchronous spontaneous and sensory evoked inputs. These results were
further supported in awake mice, where we recorded the excitatory inputs of
individual cortical cells simultaneously with the local field potential (LFP) in a
nearby site. Our results therefore indicate that cortical synchronization
emerges by intracortical coupling.
Poster #22
Olfactory bulb and piriform cortex exhibit vibrissa responses that
depend on barrel cortex activity.
Ana Parabucki, Ilan Lampl
Crucial aspect of sensory perception is that it is often a result of processes in
which multiple cues, coming from different modalities (such as visual,
auditory, touch and olfactory) are integrated into a unified concept. This
multisensory integration greatly improves the reaction time and detection of
stimuli, hence enhancing the representation of the external environment by
reducing uncertainties in sensory assessment. A large body of multisensory
integration studies indicated that most cross-modal interactions occur at high
stages of processing. However, specific tactile-auditory inhibitory interactions
were reported in the brainstem.
We found that in anaesthetized mice stimulation of the vibrissae evoked a
robust local field potential (LFP) response and elevated firing rate in the first
stage of olfactory processing – the olfactory bulb (OB). Moreover, paired
recordings showed a strong response to whisker stimulation in the piriform
cortex (PC), which precedes the onset of OB response. Pharmacological and
optogenetical inactivation of the barrel cortex substantially reduced the OB
responses. In awake animals whisker stimulation evoked no clear response in
the OB unless the animal was exposed to aversive odors. Together these
findings the existence of a novel form of multisensory integration in which topdown inputs from the primary sensory cortex of one modality (barrel cortex)
evoke robust neuronal activity at the early stage of sensory processing in
another modality (olfactory bulb).
Poster #23
Layer 6 contributes to sensory induced potentiation in somatosensory
and motor cortex
Desire Humanes-Valera, Patrik Krieger
Cortico-cortical communication has an important role in sensory processing.
To study this communication we have focused on the sensorimotor circuit of
the rodent vibrissal system. Sensory inputs were elicited by moving the
whiskers using electrical stimulation of the whisker pad. Using a 2 Hz
stimulation protocol, we induced a potentiation of whisker evoked responses
in the sensorimotor circuit. Our results show that in somatosensory cortex
(S1) responses to whisker movements, in both granular and supragranular
layers, increase after the potentiation protocol. Moreover, motor cortex (M1)
responses also increased, but only in layer 5, which is a major input layer for
S1 projections. Cortical projections originating in layer 6 in S1 have an
important function controlling columnar modulation. To study the contribution
to the observed potentiation we blocked a sub-population of L6 pyramidal
cells. Silencing the output of these layer 6 cells blocked the potentiation in
L2/3 in S1 and in L5 in M1. The potentiation can be induced by subcortical
and cortical mechanisms. In our results, we observed that the L6 blockade
interfered with the intracortically mediated potentiation, but not the direct
thalamic potentiation of layer 4, thus suggesting that silencing L6 did not
affect the subcortical mechanisms.
Poster #24
Vibrissa motor cortex activity suppresses contralateral whisker
movement
Christian L. Ebbesen, Guy Doron, Constanze Lenschow, and Michael Brecht
Anatomical, stimulation and lesion data point to a role of vibrissa motor cortex
in the control of whisker movement. Motor cortex is classically thought to play
a key role in movement generation, but most studies have found only weak
correlations between vibrissa motor cortex activity and whisking. The exact
role of vibrissa motor cortex in motor control remains unknown. To address
this question we recorded vibrissa motor cortex neurons during various forms
of vibrissal touch, all of which were associated with increased movement and
forward positioning of whiskers. Free whisking, palpation of objects and social
touch all resulted in similar vibrissa motor cortex responses: (i) Population
activity decreased. (ii) The vast majority (~80%) of significantly modulated
single cells decreased their firing. (iii) Rate-decreasing cells were the most
strongly modulated cells. To understand the cellular basis of this decrease of
activity, we performed juxtacellular recordings, nanostimulation and in vivo
whole-cell recordings in head-fixed animals. Social facial touch – a strongly
engaging stimulus – resulted in decreased spiking, massively decreased cell
excitability and a ~1.5 mV hyperpolarization in vibrissa motor cortex neurons.
To assess how activation of vibrissa motor cortex impacts whisking we
performed intracortical microstimulation, which led to whisker retraction, as if
to abort vibrissal touch. Finally, we blocked vibrissa motor cortex. A variety of
inactivation protocols resulted in increased contralateral whisker movements
and contralateral whisker protraction, as if to engage in vibrissal touch.
Surprisingly, our observations collectively point to movement suppression as
a prime function of vibrissa motor cortex activity.
Poster #25
Air-Track: A real-world floating environment for active sensing in headfixed mice
Mostafa A. Nashaat, Hatem Oraby, York Winter, Robert N. S. Sachdev,
Matthew E. Larkum
Natural behavior occurs in multiple sensory and motor modalities. These
multimodal behavioral interactions are embodied in the various iterations of
the head-fixed rodent stepping on a treadmill or walking on an air ball while
navigating a virtual reality, or discriminating between somatosensory stimuli. A
goal of these new developments is to elicit natural behavior by mimicking a
quasinatural environment and to study the effect of locomotion on cortical
responses at the cellular level. Here we have developed an “Air-Track” where
head-fixed mice navigate a real environment. The environment has walls in
the shape of a small plus maze, and surfaces for the animal to discriminate
with whiskers or both. The Air-Track system combines a virtual reality – the
animal is moving an Air-Track, but is not physically moving itself— and a
physical reality, where movement by the mouse positions physical
discriminanda that mouse uses in making decisions. In a two alternative
forced choice task, the animal moves the Air-Track back and forth and rotates
the maze from lane to lane, performing contextual behavior. In the course of
this behavior, whisker and paw movement can be tracked in a newly
developed online method. The track design can be modified and used to
study decision-making quantitatively in quasi-natural complex environments.
With the Air-Track, we come closest to providing a real environment for
eliciting the natural behavior of mice in closed spaces.
Poster #26
Multidimensional response correlations enhance population code
reliability and allow prediction of single trial noise in mouse visual
cortex
Jorrit S. Montijn, Guido T. Meijer, Carien S. Lansink, Cyriel M.A. Pennartz
Sensory neurons are often tuned to particular stimulus features, but their
responses to repeated presentation of the same stimulus can vary greatly
over subsequent trials. This presents a problem for understanding the
functioning of the brain, as downstream neuronal populations ought to
construct accurate stimulus representations, even upon singular exposure. To
study how trial-by-trial fluctuations (i.e., noise) in neuronal activity influence
cortical representations of sensory input, we performed chronic imaging of
GCaMP6-expressing populations in mouse V1 and observed that higherdimensional response correlations within local populations can be used to
predict single-trial, single-neuron noise. These multidimensional correlations
are structured such that variability in the response of single neurons is
relatively harmless to the population representation of grating orientation and
natural movies. We propose that multidimensional coding may represent a
canonical principle of cortical circuits explaining why the apparent noisiness of
neuronal responses is compatible with accurate neural representations of
stimulus features.
Poster #27
Organization of Barrel Cortex Layer 5B subcortical projections
Anton Sumser, Bert Sakmann and Alexander Groh
Neurons in cortical layer 5B (L5B) connect the cortex to various subcortical
areas. Possibly the best-studied L5B cortico-subcortical connection is formed
between L5B neurons in barrel cortex (BC) and the posterior medial nucleus
of the thalamus (POm). L5B neurons form sparse but powerful giant synapses
which can drive target POm via giant EPSPs (>10mV). Much less is known
about the organization of L5B giant boutons in other parts of the brain. A
complete target map of L5B neurons in barrel cortex is missing and it is
unclear if L5B cortico-subcortical pathways retain somatotopic, i.e. body map
organization. By dual, small and non-overlapping anterograde viral tracer
injections in deep layers of BC, we labeled cortical bouton fields in the whole
brain. Subsequent large-scale confocal scanning microscopy and slice
alignment enabled us to semi-automatically reconstruct the projection fields of
two adjacent BC L5B areas for each experiment. In total we extracted and
reconstructed the 3D location of approximately 3 million large profiles from
seven such dual injection experiments. We found that L5B in BC targets 13
subcortical areas (7 in thalamus, 5 in brainstem, 1 in midbrain). Bouton
numbers, density and projection volume varied greatly between nuclei.
However, in all investigated areas we consistently found somatotopic
segregation of the projections from different barrel columns in BC, albeit with
varying precision. In conclusion, corticofugal L5B targets many subcortical
structures via sparse but somatotopically organized pathways.
Poster #28
Correlation between Cortical State and Locus Coeruleus Activity:
Implications for Sensory Coding in Rat Barrel Cortex
Zeinab Fazlali, Yadollah Ranjbar-Slamloo, Mehdi Adibi and Ehsan Arabzadeh
Locus Coeruleus (LC) neuromodulatory nucleus in the brainstem is known to
modulate the activity of individual cells as well as global brain state. Here, we
quantified the link between spontaneous LC activity, cortical state and
sensory processing in the rat Barrel Cortex (BC). Under urethane anesthesia,
we simultaneously recorded unit activity from LC and BC along with prefrontal
EEG while presenting brief whisker deflections of various amplitudes. The
ratio of low to high frequency components of EEG (referred to as the L/H
ratio) identified the cortical state. We found that spontaneous activity of all
recorded units in LC exhibited a negative correlation with the L/H ratio. Crosscorrelation analysis revealed that changes in LC firing rate preceded changes
in state: the cross-correlation function between LC firing profile and L/H ratio
showed the strongest correlation at -1.2 s. We further quantified BC neuronal
responses to whisker stimulation during the synchronized (high L/H ratio) and
desynchronized (low L/H ratio) states. In the desynchronized state, BC
neurons showed lower stimulus detection threshold, lower trial-to-trial
variability, and shorter response latency. The most prominent change in BC
response was observed during the late phase of evoked activity (100-400 ms
post stimulus onset): the desynchronized state significantly increased the late
response almost for every recorded BC unit. These findings provide evidence
for the involvement of the LC norepinephrine neuromodulatory system, in
desynchronization of cortical state and a consequent enhancement of sensory
coding efficiency.
Poster #29
Somatosensory Processing and Plasticity Deficits in Mouse Barrel
Cortex
Project #1: Konrad Juczewski, Helen von Richthofen, Claudia Bagni, Tansu
Celikel, Gilberto Fisone, Patrik Krieger
Project #2: Stuart D. Greenhill, Konrad Juczewski, Annelies de Haan, Gillian
Seaton, Kevin Fox, Neil R. Hardingham
Touch is an important source of sensory information. Disturbances to the
development of the somatosensory system have serious consequences for
social behavior and may lead to many neurodevelopmental disorders. In our
studies we used two different mouse models of disease: Fmr1 KO mouse with
a knock out gene Fmr1 (a model of fragile X syndrome); and DISC1-cc
transgenic mouse with transient disruption of signaling (DISC1 is a molecule
implicated in psychiatric disorders). In Fmr1 KO mice we focused on
analyzing somatosensory processing defects that lead to hypersensitivity to
touch in Fragile X Syndrome (FXS) patients. We show neuronal mechanisms
that appear to underlie hypersensitivity to somatosensory stimuli (whisker
deflections) thus causing an altered behavior observed in Fmr1 KO mice. In
addition we provide evidence showing how the processing and encoding of
tactile information have been affected. In DISC1-cc mice we activated
truncated protein DISC1-cc for a controlled period of time at different points
during the early postnatal development. Development is shaped by sensory
experience, especially during phases known as critical periods. Disruption of
experience during a critical period normally produces neurons that lack
specificity for sensory experience in adulthood. We found that transient
disruption of DISC1 signaling during a critical period of development produced
neurons that lack plasticity in adulthood. Adult plasticity deficits may be
associated with cognitive deficits and the delayed onset of psychiatric
symptoms in late adolescence. Using the whisker system as a model system
we have obtained insight into potential disease mechanism causing human
brain disorders.