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Cerebral Cortex - Basic Cell Types
NEOCORTEX-BASIC NEURON TYPES
Maria Toledo-Rodriguez1, Anirudh Gupta1, Yun Wang2, Cai Zhi Wu1 and Henry Markram1*
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Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel
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Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06520-8001, USA
Short Title: Neocortical Cell Types
* Correspondences should be addressed to:
Henry Markram, Department of Neurobiology, Weizmann Institute of Science, 76100, Rehovot, Israel
Tel: +972-8-934-3179; Fax: +972-8-934-4131; e-mail: [email protected]
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INTRODUCTION
The neocortex is functionally parcellated into vertical columns (~0.5mm in diameter) traversing all layers (layers IVI). These columns have no obvious anatomical boundaries and the topographic mapping of afferent and efferent
pathways probably determines their locations and dimensions as well as their functions (Peters and Jones, 1984;
White, 1989). Multiple columns overlap, suggesting that the underlying neural microcircuits are designed to enable
universal computation. These apparently omnipotent and stereotypical microcircuits are composed of a daunting
variety of precisely and intricately interconnected neurons (Douglas and Martin, 1998; Somogyi, 1998; White 1989),
that differ in terms of their anatomical, electrophysiological, and molecular properties (Cauli et al., 1997; DeFelipe,
1993; Gupta et al., 2000; Kawaguchi and Kubota, 1997; Peters and Jones, 1984; Thomson and Deuchars, 1997).
This neuronal diversification may provide a foundation for maximizing the computational abilities of the neocortex.
BASIC NEURON TYPES - ANATOMY
Excitatory Neurons
Excitatory neurons constitute by far the majority of neocortical cells (70-80%) and consist mainly of two types of
neurons (Peters and Jones, 1984; Somogyi, 1989; White, 1989):
•
Pyramidal Cells (PC; Fig 1A1), the most commonly occurring neocortical neuron (located in layers II-VI), are
characterized by a single, prominent, vertically oriented dendrite emerging from the apex of their mainly
pyramidal-shaped somata (apical dendrite), several (~4-6) more or less horizontally radiating basal dendrites,
and long descending axons that project to other cortical and subcortical areas. The apical dendrite traverses
through several layers, allowing PCs to sample multiple layer-specific inputs, before fanning out into a terminal
tuft (often reaching layer I). The basal dendrites mainly remain within the layer of the cell body (sometimes
entering adjacent layers), spanning the full diameter of the cortical column. PC-axons give rise to a local
columnar cluster that may spill over into neighboring columns before continuing to the white matter.
Additionally, long vertical and horizontal collaterals project across layers and columns, sometimes forming
secondary axonal clusters. PCs are therefore “local circuit neurons” as well as “projection neurons”.
•
Spiny Stellate Cells (SSC; Fig 1A1), found almost exclusively in layer IV of the primary sensory areas, are
characterized by multiple short dendrites (contained within a layer and column) radiating from spherical somata
(stellate appearance). Their axons produce a local axonal cluster of columnar extent within layer IV, before
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projecting either loosely or in tight bundles to arborize extensively in layers II/III. Some collaterals descend
towards layers V/VI. SSCs are mainly “local circuit neurons”, although in few cases they have been shown to
project to other cortical areas (Douglas and Martin, 1998).
Whereas PCs and SSCs are easily distinguished by multiple morphological features, both types of excitatory neurons share
several functional properties, that have been amply used to distinguish them from inhibitory neurons (White, 1989): (i)
their dendrites are typically densely studded with small membranous protuberances known as spines (hence they are also
known as spiny neurons; see - DENDRITIC SPINES – Holmes); (ii) they release glutamate from their presynaptic
terminals (boutons), that form asymmetric (excitatory) synapses mainly onto the spines of other excitatory neurons (see –
CHEMICAL AND ELECTRICAL SYNAPSES IN NEOCORTEX – Gibson & Connors); (iii) their somata invariably
receive only symmetrical (inhibitory) synapses.
Inhibitory Neurons
Inhibitory neurons constitute 20-30% of the neocortical cells and are highly heterogeneous (Peters and Jones, 1984;
Somogyi, 1989; White, 1989; Fig 1A2-5). They are easily distinguished from excitatory neurons by their lack of an
apical dendrite, low spine densities (hence they are also known as smooth and/or sparsely spiny neurons), beaded
dendrites and axonal arbors that remain almost exclusively within a column (hence they are also known as local
circuit neurons or interneurons; but see exceptions below). Instead of an apical dendrite projecting towards the pia,
many interneurons have a prominent dendrite (with more branches) extending towards the white matter (WM).
Moreover, the initial course of their axons, which either originate from the soma or a primary dendrite, is often
towards the pia (instead towards the WM, which characterizes the axon trajectory of excitatory neurons). Inhibitory
neurons release GABA at their symmetric synapses and their cell bodies invariably receive both excitatory and
inhibitory synapses. Most types of interneurons may display various soma shapes (ovoid, spindle-shaped, triangular,
inverted pyramidal) and dendritic morphologies (bipolar, bitufted and multipolar), but each type characteristically
displays unique features in its axonal structure. Details of the axonal arborization (White, 1989), as well as the
preferential placement of synapses onto different target-cell domains (Somogyi, 1989; Somogyi et al., 1998), have
therefore provided the foundation for classifying interneurons. This selective innervation allows each type of
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interneuron to effect its target cells in a compartment-specific and potentially independent manner (see PERSPECTIVE ON NEURON MODEL COMPLEXITY - Rall). Inhibitory neurons that selectively innervate:
•
the (peri-) somatic region of their target cells, may affect the strength and gain of summated synaptic potentials
(see - SINGLE-CELL MODELS- Koch, Mo & Softky), the timing of action potential (AP)-generation and
hence the concerted action of populations of target cells (see -SYNCHRONIZATION OF NEURONAL
RESPONSES - Singer).
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the dendrites of their target cells, may influence dendritic processing and integration of synaptic inputs (see DENDRITIC PROCESSING – Segev & London), generation and propagation of dendritic APs, and synaptic
plasticity (see – HEBBIAN SYNAPTIC PLASITICITY - Fregnac).
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the axon initial segment of their target cells, may affect both the generation and the “gating” of APs (see AXONAL MODELING - Koch & Bernader).
Most interneuron types, although mainly studied in layers II-V, are also found in layer VI, whereas layer I
is characterized by its own distinct set of interneurons (see below). Moreover, it is currently not known, whether
additional subtypes, specific to layer VI exist, although this lamina is characterized by a multitude of ill-defined
local circuit neurons (~8-12 types) that still await precise description (Peters and Jones, 1984). The following
describes the most common types of interneurons located in rat somatosensory cortex (layers II-V), based on a very
large data set with considerable emphasis on quantitative morphometric analysis (see for example, Wang et al.,
2002). These basic interneuron types are found across different neocortical areas and species. Minor structural
variations of these interneuron types (depending on neocortical layers, regions, age and species) will not be
considered here.
Interneurons that preferentially target somata and proximal dendrites
Basket cells (BCs), probably the most frequently encountered neocortical interneurons, are distinguished by their
preferential innervation of somata (20-40%) and proximal dendrites (onto shafts and spines) (Kisvarday, 1992). BCs
in general give rise to several beaded, mainly aspiny, dendrites. They are composed of three main subclasses, that
differ in the structure of their axonal arborizations (Wang et al., 2002), each of which appears to be differentially
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distributed throughout layers II-VI.
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Large Basket Cells (LBC, Fig. 1A2) produce a sparse local, mainly intralaminar and –columnar, axonal
cluster composed of few, long and straight branches of low bouton density (BD) before generating their
characteristic conspicuous long-range horizontal collaterals, that traverse multiple columns and some
vertically projecting collaterals that may cross all layers (Somogyi, 1989). LBCs are therefore “local
circuit” as well as inhibitory “projection” neurons.
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Small Basket Cell (SBC, Fig. 1A2) give rise to a characteristic dense local, intralaminar and –columnar,
axonal cluster composed of frequent, short, and curvy axonal branches with high BD. Occasionally SBCs
may generate a few far-reaching collaterals projecting across layers and columns. A special subtype of
SBC, termed Clutch Cell, has been observed in layer IV of the visual cortices of cat/monkey (Kisvarday,
1992). These cells are medium sized, multipolar cells that typically produce large bulbous terminals, which
often “clutch” somata of their target cells.
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Nest Basket Cell (NBC, Fig. 1A2) give rise to a sparse to dense local, mainly intralaminar and –columnar,
axonal cluster composed of infrequent, long and smoothly bending axonal branches of low BD. They may
occasionally produce a few far-reaching collaterals projecting across layers and columns. In addition,
NBCs exhibit a characteristically simple dendritic arbor with few short and infrequently branching
dendrites (Gupta et al., 2000; Wang et al., 2002).
Interneurons that preferentially target dendrites
Interneurons that preferentially target dendrites, usually give rise to beaded, aspiny or sparsely spiny dendrites.
Importantly, their overall “axonal fields” are preferentially vertically oriented (except NGCs, see below).
•
Bitufted Cells (BTC, Fig. 1A3) display ovoid somata that emit two dendritic tufts from opposite poles that are
preferentially vertically oriented and may emit an additional oblique dendrite (Somogyi, 1989). Their axonal
arborizations are characterized by long, vertically oriented collaterals of low BD that may extend through all
layers and mainly branch in a bifurcating manner. Their axonal ramification is mostly intracolumnar, although
in some cases they may extend into neighboring columns.
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Bipolar Cells (BPC, Fig. 1A3) typically produce the simplest dendritic and axonal arborization of all
interneurons, as both dendrites and axons branch very infrequently at shallow angles. The two long, vertically
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oriented, primary dendrites of BPCs are emitted from the opposite poles of their small spindle-shaped somata,
and may span all cortical layers occasionally forming a dendritic tuft in layer I (Peters and Jones, 1984). The
axon of BPCs typically emerges from a primary dendrite (usually the lower dendrite) before ramifying
vertically across multiple or all layers. It is characterized by a very low number of boutons that are typically
placed onto the dendritic shafts of rather restricted population of target neurons. Some BPCs in layers II-V have
been shown to form asymmetrical synapses, preferentially onto spines, suggesting that they are excitatory
(eBPCs, not shown; White, 1989).
•
Double Bouquet Cells (DBC, Fig. 1A3) are interneurons that like BPCs appear to consist of two classes.
Inhibitory DBCs, that appear to be preferentially located in layers II/III, display bitufted or multipolar dendritic
morphologies and typically produce a thin axon that bifurcates to give rise to a characteristic, mainly
descending, “horsetail-like”, tight fascicular axonal bundle. The collaterals forming these narrow columnar
bundles of high BD are typically much thicker than the main stem, and may extend across all layers. A local
axonal ramification of different densities may occasionally be formed. Some double bouquet cells in layers II-V
that generate both ascending and descending axonal collateral bundles have been shown to form asymmetrical
synapses onto target cells, suggesting that they are excitatory (eDBCs, not shown; White, 1989).
•
Neurogliaform Cells (NGC, Fig. 1A3) are very small cells that produce dense, spherical dendritic and axonal
fields confined within a single layer and column (densest fields of all interneuron types). They typically produce
a large number of thin, radiating dendrites that are short, aspiny, finely beaded and rarely branched. Their very
thin axons, branches intricately to produce a very dense and highly intertwined arborization (spiderweb-like
appearance) that is studded with tiny boutons. NGCs target mainly dendritic shafts (Somogyi, 1989) and are
also found in layer I.
Interneurons that preferentially target dendrites and dendritic tufts
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Martinotti Cells (MC, Fig. 1A4) display a more elaborate dendritic arbor than most interneurons, which is
formed by beaded and sparsely- to medium-spiny dendrites. Their local and quite dense axonal cluster
(mainly intralaminar and intracolumnar) is formed by collaterals that branch at wide angles before
projecting up to layer I, where they spread across many columns, forming spiny boutons. MCs are “similar”
to LBCs in that they are “local circuit” as well as inhibitory “projection” neurons. However, due to their
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innervation of distal dendrites and tufts, the form of their inhibitory impact is expected to differ
substantially from that of LBCs.
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Neurons exclusive to layer I are believed to mainly innervate the dendritic tufts of target neurons and
encompass several interneuron types. Cajal-Retzius Cells (CRC, Fig. 1A4) display large somata, long
horizontal dendrites and horizontally projecting axons, which characteristically give rise to numerous short
ascending and some descending, terminal fibrils. Small layer I cells (not shown) are neurons with short
processes that constitute a heterogeneous group of multipolar interneurons with varying axonal
arborizations. These have been subdivided into small neurons with poor or rich axonal plexus, respectively
(Peters and Jones, 1984).
Interneurons that preferentially target axons
•
Chandelier Cells (ChC, Fig. 1A5) are characterized by a local axonal cluster with a “chandelier-like”
appearance resulting from the terminal axonal portions forming short vertical bouton arrays (“candlesticks”)
onto the axon initial segments of target neurons (mainly PCs; Somogyi et al., 1998). Their local axonal clusters
- mainly confined within a single layer and column - are formed by collaterals of high BD that frequently
branch at shallow angles. ChCs give rise to mostly aspiny, beaded, infrequently branching dendrites that may
span one or several layers.
BASIC NEURON TYPES - ELECTROPHYSIOLOGY
Neocortical neurons display diverse intrinsic electrophysiological properties that result mainly from differences in
their ion channel composition and constellation. Ion channels are state-dependent and therefore a neuron’s passine
and active properties may change according to different conditions (see ION CHANNELS, KEYS TO NEURONAL
SPECIALIZATION- Bargas et al.). However, for standardized stimulation and recording conditions, neuronal
discharge responses are stable and can serve as a reliable “marker” of their biophysical identity.
Electrophysiological diversity indicates that identical spatio-temporal patterns of synaptic inputs will be
differentially integrated and transformed into fundamentally different AP-patterns (and hence different synaptic
outputs) and may therefore profoundly increase the computational repertoire of neural circuits (see –
COMPUTATIONS WITH SPIKING NEURONS – Maass).
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Excitatory Neurons
Excitatory neurons have been shown to display limited diversity in their discharge responses. Differences in their
discharge properties have been described by three distinct features: (i) kinetic properties of single APs, (ii) discharge
response to intrasomatic threshold and (iii) supra-threshold current injections (Amitai and Connors, 1995; Connors
and Gutnick, 1990; see Table 1). Discharge responses to supra-threshold current injections have proven to be the
most useful parameter in distinguishing subclasses of both excitatory as well as inhibitory neurons (see below).
By far the most common discharge response observed for both PCs and SSCs has been described as
regular-spiking (RS, see Fig 1B1). Sustained supra-threshold currents cause these cells to fire repetitively with a
progressive decrease in firing frequency [progressive increase in inter-spike intervals (ISIs)], generally referred to as
spike train adaptation or accommodation. Differences in the degree of accommodation, have led to subclassification
into RS1 (weak accommodation; most common behavior; see Fig 1B1) and RS2 cells (strong accommodation;
behavior of PC- and SSC- subpopulations, see Table 1) (Connors and Gutnick, 1990). Some PCs and SSCs have
been shown to display intrinsic bursting behavior (IB; not shown; see Connors and Gutnick, 1990). These neurons
discharge with a cluster of three to five APs riding on a slow depolarizing wave (referred to as a burst), followed by
an after-hyperpolarization, and then by either single spikes or bursts at more or less regular intervals (referred to as
regular spiking and repetitive bursting, respectively). Other much less common discharge behaviors have been
observed for subpopulations of PCs (see Table 1), including chattering (CHTs; not shown; see Gray and
McCormick, 1996) and rhythmic firing (RF; not shown; see Amitai and Connors, 1995). CHT-cells usually display
repetitive long clusters of APs to sustained supra-threshold current injections that, when made audible, sound like
chattering. RF-cells discharge continually without accommodation.
Inhibitory Neurons
Inhibitory neurons display a much larger repertoire of discharge behaviors compared to excitatory neurons (see Fig
1B2, see Table 1), and their electrophysiological (sub-) classification has been gradually refined over the last
decade. Initially only a single discharge behavior, known as fast-spiking (FS), was described for smooth or sparsely
spiny neurons throughout layers II-VI. FS-cells generate single APs with characteristics distinct from that of spiny
(excitatory) neurons (faster rise rates (RR) and fall rates (FR), distinct fast afterhyperpolarizing potentials (fAHP);
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see Connors and Gutnick, 1990) and discharge repetitively at high frequencies with little or negligible
accommodation to sustained supra-threshold currents. Since other discharge behaviors were not observed initially
for smooth cells, it was believed, that interneurons represent a homogenous population of characteristically fastspiking (referring to both the brevity of single APs and the resulting high discharge rate) neurons. Subsequent
studies, mainly carried out in layers II/III and V, however, gradually demonstrated, that interneurons could display
several other discharge patterns: (i) burst spiking non-pyramidal cells (BSNP) originally described as low-threshold
spiking cells (LTS), typically display burst-like discharges after a hyperpolarizing pre-pulse (see Kawaguchi and
Kubota, 1997); (ii) late-spiking cells (LS) respond with a slow ramp depolarization and a late onset of discharge
after a step current pulse (see Kawaguchi and Kubota, 1997); (iii) regular spiking non-pyramidal cells (RSNP)
displaying discharge patterns similar to the RS response of PCs (see Kawaguchi and Kubota, 1997); and (iv)
irregular spiking cells (IS) typically discharge with an initial burst of APs followed by an irregular spiking response
(Cauli et al., 1997). IS cells have been further divided into two subclasses (IS1 and IS2) according to the duration of
the initial burst.
Attempts to assign distinct electrophysiological discharge patterns to specific anatomical interneuron types
have been made (Kawaguchi and Kubota, 1997; Thomson and Deuchars, 1997). Unfortunately, in many cases, the
precise morphological identites of the electrophysiologically classified neurons could only be determined in
fractions of the recorded cells: Some MCs and DBCs were shown to display BSNP-behavior, whereas LS-behavior
was observed for some NGCs and IS-behavior for some interneurons with bipolar morphology (Cauli et al., 1997).
Finally, DBCs, MCs and BPCs may also display RSNP-behavior, indicating that the same anatomical type may
display more than one discharge pattern (see Table 1).
Interneuron discharge patterns, however, display an even richer diversity of behaviors. Recent studies –
aimed at understanding the functional position of a large number of morphologically identified interneurons within
the neocortical microcrocuitry - adopted a simple classification scheme that encompasses previous schemes (Gupta
et al., 2000; see Table 1) and considers both the steady-state and the onset response to sustained somatic current
injections (Fig 1B2). According to this scheme, neocortical interneurons are categorized into 5 main classes with 3
subclasses each, according to the discharge response at steady-state and onset phase, respectively. These
interneuronal discharge patterns are stable for (i) different baseline membrane potentials and (ii) durations and
amplitudes (several times threshold) of step current injections (see Gupta et al., 2000; Wang et al., 2002):
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non-accommodating cells (NAC, Fig 1B2) fire repetitively without frequency accommodation (no or
minimial change in ISIs). The steady-state discharge frequency increases steeply as a function of the
injected current amplitude, allowing NAC cells to reach very high firing frequencies. Their APs are very
brief and characteristically display a deep fAHP. NACs are the most frequently encountered cells in all
layers
•
accommodating cells (AC, Fig 1B2) fire repetitively with a decrease in discharge frequency (the gradual
increase in ISIs preventing high firing rates) and are the second most frequently observed
electrophysiological class.
•
stuttering cells (STUT, Fig 1B2) fire high frequency AP-clusters (with no or minimal accommodation)
intermingled with unpredictable periods of silence (“morse-code”-like discharges). Cells displaying
stuttering near threshold and fast spiking at slightly higher depolarizations, are not considered STUTs.
•
irregular spiking cells (IS, Fig 1B2) discharge single APs in a random manner throughout a depolarizing
pulse, but do not form distinct clusters of APs.
Each of these main classes displays an array of stereotypical onset responses, which have been used for
subclassification. They either discharge with:
•
a burst (a high frequency cluster of three or more APs), that seamlessly merges into the steady-state
response (b-subclass; see Fig 1B2).
•
a distinct delay before discharging to a current pulse (d-subclass; see Fig 1B2). The duration of the delay
decreases progressively as the amplitude of current injection increases. Delayed discharging cells
characteristically show significantly higher action potential thresholds than the b- and c-subclasses.
•
neither a burst nor a delay (referred to a classical response). The “onset” phase of these cells (c-subclass;
see Fig 1B2) is therefore indistinguishable from the steady-state phase.
A fifth main class of bursting cells (BST; less frequent than the above main classes), with 3 subclasses, was
recently observed (not shown). The onset response of BST-cells is characterized by a high frequency cluster of three
to five APs riding on a slow depolarizing wave followed by a strong slow AHP, that causes a clear separation of the
onset burst response from the consecutive steady-state responses, even at high current injections. The peak
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amplitudes of these APs decrease during the bursts in most cells. These burst properties differ fundamentally from
those that define the b-subclasses of NAC-, AC-, STUT- and IS-cells. BST-cells may be subclassified according to
their steady-state discharge response into
•
r-BST cells, that characteristically discharge repetitive burst (r = repetitive)
•
s-BST cells, that characteristically fail to discharge after their initial burst due to a more pronounced,
complex of powerful AHP (s = single).
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i-BST cells, that characteristically discharge an accommodating train of APs (i = initial).
Recent computational studies have addressed the mechanisms of bursting behavior in neocortical PCs (see OSCILLATORY AND BURSTING PROPERTIES OF NEURONS – Wang & Rinzel). Similar studies for the other
types of discharge behaviors in both excitatory and inhibitory neurons are eagerly awaited, especially in light of the
profound effects, that different discharge properties may have on the behavior of neural circuits (i.e. van Vreeswijk
and Hansel, 2001).
BASIC NEURON TYPES - MOLECULAR
Neocortical neurons express a variety of intracellular molecules including classical neurotransmitters (glutamate,
GABA, acetylcholine and catecholamines), neuropeptides, calcium binding proteins (CaBPs), as well as a multitude
of different cell-surface molecules (neurotransmitter receptors, etc.). While these molecular species are found
throughout the neocortex, each neuron only expresses some of these molecules and in specific combinations
(DeFelipe, 1993), allowing the use of expression and co-expression patterns for neuronal classification. Of these
“molecular markers”, the (co-) expression of the most common CaBPs (calbindin, CB, parvalbumin, PV and
calretinin, CR) and neuropeptides (neuropeptide Y, NPY, vasoactive intestinal peptide, VIP, somatostatin, SOM,
cholecystokinine, CCK) has been most extensively studied (Cauli et al., 1997; DeFelipe, 1997; Kawaguchi and
Kubota, 1997; Wang et al., 2002). The functional significance of this molecular diversity is currently not fully
understood, although some of the above mentioned “markers” (i.e. synaptically released neuropeptides) have been
implicated in modulating synaptic transmission and/or neuronal excitability.
Table 2 summarizes molecular expression profiles of neocortical neurons (mainly layers II-VI; except
CRC, see above) for the most commonly investigated CaBPs and neuropeptides, based on studies of protein- or
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mRNA- expression (mainly rodent neocortex). Whereas every molecular expression profile detected at the protein
level has been confirmed at the mRNA level, some mRNA-expression profiles have not been detected at the protein
level (compare Cauli et al, 1997; Wang et al, 2002 with Kawaguchi and Kubota, 1997). In general, neocortical
excitatory neurons (mainly PCs) have been shown to differ from inhibitory neurons, (i) in that the percentage of PCs
expressing CaBPs and/or neuropeptides is considerably lower and (ii) in that they typically display a much more
restricted set of expression profiles.
DISCUSSION
The present chapter outlines the main properties defining the basic cell types in the neocortex. The most striking
feature of neocortical neurons is their immense anatomical, electrophysiological and molecular diversity. All
anatomical cell types can display multiple discharge patterns and molecular expression profiles. Different cell types
are synaptically interconnected according to complex organizational principles to form intricate stereotypical
microcircuits. It is still unknown how afferent and efferent pathways determine the locations, dimensions and
functions of these seemingly omnipotent microcircuits that underlie the formation of functional columns. The major
challenge for neural network models is to incorporate and account for the cellular diversity, which may explain the
universal computational capability of these stereotypical microcircuits.
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physiological diversity of cortical nonpyramidal cells, J. Neurosci., 17:3894-3906.
*Connors B.W., Gutnick M.J., 1990, Intrinsic firing patterns of diverse neocortical neurons, Trends Neurosci.,
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Gray C.M., McCormick D.A., 1996, Chattering cells: superficial pyramidal neurons contributing to the generation of
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*Gupta A., Wang Y., Markram H., 2000, Organizing principles for a diversity of GABAergic interneurons and synapses
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*Kawaguchi Y., and Kubota Y., 1997, GABAergic cell subtypes and their synaptic connections in rat frontal cortex,
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Figure and Table Legends
Figure 1: Anatomical and Electrophysiological Diversity of Neocortical Neurons. A: Scheme summarizing the main
anatomical properties of neocortical excitatory (A1) and inhibitory (A2-5) neurons. Each neuron type labeled by 3-letter
abbreviation (for explanation, see text). Dendrites: thick, light gray; axon: thin, black lines; black dots: axonal boutons.
Spines omitted for clarity. Neurons oriented with pia facing upwards and white matter (WM) downwards. Note the
presence of a prominent, vertical dendrite directed towards WM on some interneurons (A2-4). Inhibitory interneurons
(A2-5) are mainly distinguished by the structure of their axonal arbor (see text) and typically innervate selective domains
[A2: (peri-) somatic; A3,4 dendritic; A5: axonal] of their target cells. B: Representative samples of the most common
discharge responses of neocortical excitatory (B1) and inhibitory (B2) neurons to standardized intrasomatic step-current
injections. B1: Excitatory cells typically display regular-spiking (RS) discharge behavior. B2: Inhibitory interneurons
display a vast repertoire of discharge responses, displaying either bursts (b-), delays (d-) or neither burst/delay (classical,
c-) at step-onset, and accommodation (AC), non-accommodation (NAC), stuttering (STUT) or irregular spiking (IS) at
steady-state. Scale bar (20 mV; 500ms) applies to all traces.
Table 1: Electrophysiological Classes of Neocortical Excitatory and Inhibitory Neurons. Interneuron
classification: main classes and subclasses defined according to discharge responses at steady-state and onset-phase
to intrasomatic current injections, respectively (see text, see Fig 1B2). Abbreviations explained in text; nd: not
determined/detected so far; (*) morphological types listed according to sequence of description in text and not
according to frequency of occurrence; (**) some authors have suggested to distinguish between accommodating FScells (FS-cells) and non-accommodating FS-cells (classical FS-cells or CFS; see Thomson and Deuchars, 1997).
Table 2: Molecular Classes of Excitatory and Inhibitory Neocortical Neurons. Excitatory neurons (shown to
express glutamate) and inhibitory neurons (shown to express GABA or GABA producing enzymes GAD 65 and/or
GAD 67), located throughout layers II-VI, have been sorted according to the detection of CaBPs, neuropeptides and
their co-expression. Abbreviations explained in text. In all cases listed, consistent expression profiles have been
determined at both the protein and mRNA level, except (*), in which co-expression of SOM and PV was only
detected at the mRNA level (compare Cauli et al, 1997; Wang et al, 2002 with Kawaguchi and Kubota, 1997). Note
Markram_H.
Cerebral Cortex - Basic Cell Types
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that the expression profiles are listed separately for either the anatomical or electrophysiological identities of the
inhibitory neurons. Detailed information regarding expression profiles of SSCs not available to date.