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October 2008
Neuroscience Journal Club
Experience-dependent plasticity of
dendritic spines in the developing rat
barrel cortex in vivo
Balazs Lendvai*, Edward A. Stern, Brian Chen & Karel Svoboda
Processing of Sensory Informations
BRAIN: what for?
ELABORATION OF STIMULA
• COLLECTION OF (SENSORY)
INPUTS
•
PROCESSING OF INFO (Cortex)
→ RECORDING
•
SPAWNING A (MOTOR) OUTPU
Analogous to neurons processing
BRAIN: what for?
MEMORIZATION
•
ENCODING: analysis of
sensorial informations
•
STORAGE: keep a copy or
permanent recording of
coded informations
•
RETRIEVAL: following use of
the information stored, in
order to behave in a certain
way or to solve a problem.
October 2008
Where is memory stored?
• Where in the brain are
memories stored?
• How do we know this?
• How does the brain store
electrical patterns of
activity with cells?
• Lashley K.: lesioned various portion of the
cortex to localize the one responsible for
mnemonic retention
• H.M.: following a surgery, he suffered
from anterograde amnesia
• Penfield W.: electrical stimulation of
cortex surface
PENFIELD
• Hebb rule for Synaptic Plasticity (1946): synaptic facilitation
can derive from each experience
• The trace (persistence or repetition of a reverberatory
activity) tends to induce lasting cellular changes that adds
to its stability and that can be retrieved several years later
through an electrical current, without loosing any detail
October 2008
The substrate of memory is:
dendritic spines – maybe…
October 2008
How is long-term memory stored?
•Neurons form circuits where
electrical signals (spikes)
propogate between synapses
•Once a circuit is stimulated,
under certain circumstances it is
easier to stimulate again
•Reverberating circuits
•Long term potentiation
•example of an electrical
stimulation causing permanent
change
•Inhibitors of protein synthesis or
calcium signals prevent LTP
Cellular mechanisms of learning and memory:
LTP and LTD
→ Repeated stimulus leaves a
TRACE
→ Nervous track repeatedly
crossed can be subjected to
LTP
→ Activation of cascade
biochemical mechanisms
that determine
STRUCTURAL
MODIFICATIONS of the
circuit itself
Cellular mechanisms of learning
and memory: LTP and LTD
From Science, 2006
→ Activation/deactivation of synapses
→ Protrusion/retraction of spines/filopodia
Do changes in neuronal
structure underlie
cortical plasticity?1,2
1. Bailey, C. H. & Kandel, E. R. Annu. Rev. Physiol. 55, 397±426 (1993).
2. Buonomano, D. V. & Merzenich, M. M. Annu. Rev. Neurosci. 21, 149±186 (1998).
Methods
• Infection of neocortical neurons in vivo with
SIN±EGFP with injection into brain parenchyma
In vivo high-resolution
imaging of barrel cortex
neurons infected with SINEGFP (Sindbis virus containing
the gene for Enhanced GFP).
• Sensory deprivation: trimming
• Intracellular recording in vivo
Methods
• Time lapse two photon microscopy
• In vivo imaging of the structural dynamics of dendritic
spines and filopodia in the intact brain
• Piramidal neurons in layer 2/3 of developing (P8-18) rat
barrel cortex
Objectives
•Modulating sensory inputs by trimming whiskers changes
the response properties of neurons.
•Examine the effects of the rat's sensory experience on the
structure and dynamics of spiny protrusions as a substrate
of experienced-dependent plasticity
Barrel Cortex
Spatial arrangement of the whiskers on the rat’s
face : matrix of large hairs represented in these
brain areas by a topographically similar matrix
of cell rings. (A, B)
Barrels: aggregates of cell rings in layer IV of
the cerebral cortex . Barrel cortex: area in the
somatosensory cortex (C) where neurons are
grouped in barrel- like arrangements, with a
hollow center of lesser cell density surrounded
by a circle of higher cell density.
IMP: one-to-one relationship between each
vibrissa and its corresponding barrel.
Barrel Cortex 2P Time-lapse Imaging
• Characterization of dendritic protrusions: high resolution 2PLSM
images.
• Quantification of motility: lenght of individual protrusions vs time
• Description of structural dynamics for individual protrusion: average
change of lenght per sampling interval (mm per 10 min)
Results
• High mobility in vivo: dendritic protrusions are dynamic
(changed lenght, shape, appeared/disappeared) over
timescales of 10 min and over lengths of mm
• Largest motility in the youngest animals (P8-12)
→ less filopodia
Effects on the structure and dynamics of spiny
protrusions
• Whiskers trimming 1-3 days before
imaging
• Comparison of LOCATIONS:
control, deprived, specificity
• Comparison of AGES:
during (P11-13), before (P8-10),
after (P14-16) synaptogenesis
(whiskers’ use in exploratory
behaviour)
DYNAMICS
• Protrusive motility is
modulated by previous
experience
• AGE: only during a brief
critical period, P11±13,
deprivation caused a large
decrease in motility
• LOCATION: effects of sensory
deprivation are specific to the
deprived region of the cortex.
STRUCTURE AND DENSITY
Sensory deprivation does
NOT change the average
structure (distributions of
lengths, distr. among
different morphological
classes) or density of
dendritic protrusions (in
all ages)
Effects on the development
of receptive fields
•
•
Recordings of membrane potential dynamics of regular spiking neurons
in P14±16 rats
Measurement of PSPs amplitudes in response to deflections of single
whiskers (SW or PW)
RESULTS:
•
•
Principal whisker response was smaller than in control animals but the
surround was stronger and broader
Sensory deprivation has a profound effect on the TUNING of sensory
maps of layer 2/3 pyramidal neurons.
Effects on network synaptic activity
• Measurement and computation of the distribution of MP to see
if experience-dependent changes in spontaneous synaptic
activity drive changes in protrusive motility
RESULTS:
• NO long-lasting effects on network synaptic activity
• Experience-dependent changes in motility are coupled more
directly to the history of sensory activity
Results: summary
• HIGH BASAL motility in spines and filopodia: they
appeared, disappeared or changed shape over tens of
minutes
• Experience-dependent modulation of dendritic motility
(synaptic lifetimes) is limited to a sharp critical period
(P11±13)
• Does sensory experience drive this motility?
Yes: Sensory deprivation markedly (40%) reduced
protrusive motility in deprived regions of the barrel
cortex
No: Whisker trimming did NOT change the density, length
or shape of spines and filopodia
Results: summary
ELECTROPHYSIOLOGICAL MEASUREMENTS: effects on
synaptic ACTIVITY
• Sensory deprivation spanning the critical period is
associated with defective development of layer 2/3
sensory maps
• Sensory deprivation perturbs the experiencedependent rearrangements of synaptic connections
required to form precise sensory maps
Long Term Depression
• LTP can be saturated
• You only have a finite number
of synapses
• Your brain is in danger of
getting full
• Therefore you need LTD
THANKS FOR YOUR
ATTENTION!!!