A circuit model of auditory cortex.

The mammalian sensory cortex is composed of multiple types of inhibitory and excitatory neurons, which form sophisticated microcircuits for processing and transmitting sensory information. Despite rapid progress in understanding the function of distinct neuronal populations, the parameters of connectivity that are required for the function of these microcircuits remain unknown. Recent studies found that two most common inhibitory interneurons, parvalbumin- (PV) and somatostatin-(SST) positive interneurons control sound-evoked responses, temporal adaptation and network dynamics in the auditory cortex (AC). These studies can inform our understanding of parameters for the connectivity of excitatory-inhibitory cortical circuits. Specifically, we asked whether a common microcircuit can account for the disparate effects found in studies by different groups. By starting with a cortical rate model, we find that a simple current-compensating mechanism accounts for the experimental findings from multiple groups. They key mechanisms are two-fold. First, PVs compensate for reduced SST activity when thalamic inputs are strong with less compensation when thalamic inputs are weak. Second, SSTs are generally disinhibited by reduced PV activity regardless of thalamic input strength. These roles are augmented by plastic synapses. These roles reproduce the differential effects of PVs and SSTs in stimulus-specific adaptation, forward suppression and tuning-curve adaptation, as well as the influence of PVs on feedforward functional connectivity in the circuit. This circuit exhibits a balance of inhibitory and excitatory currents that persists on stimulation. This approach brings together multiple findings from different laboratories and identifies a circuit that can be used in future studies of upstream and downstream sensory processing.

Inhibitory interneuron classes express complementary AMPA-receptor patterns in macaque primary visual cortex.

Glutamate receptors mediate excitatory neurotransmission. A very prevalent type of glutamate receptor in the neocortex is the AMPA receptor (AMPAR). AMPARs mediate fast synaptic transmission and their functionality depends on the subunit composition. In primary visual cortex (area V1), the density and subunit composition of AMPARs differ among cortical layers and among cell types. The AMPARs expressed by the different types of inhibitory interneurons, which are crucial for network function, have not yet been characterized systematically. We investigated the distribution of AMPAR subunits in macaque V1 for three distinct subpopulations of inhibitory interneurons: parvalbumin-immunoreactive (PV-IR) interneurons, calbindin-immunoreactive (CB-IR) interneurons, and calretinin-immunoreactive (CR-IR) interneurons. We found that PV-IR cells, which have previously been identified as fast spiking, show high expression of the GluA2 and GluA3 subunits. In contrast, CB-IR and CR-IR cells, which tend to be intermediate spiking, show high expression of the GluA1 and GluA4 subunits. Thus, our data demonstrate that the expression of AMPARs divides inhibitory interneurons in macaque V1 into two categories that are compatible with existing classification methods based on calcium-binding proteins and firing behavior. Moreover, our findings suggest new approaches to target the different inhibitory interneuron classes pharmacologically in vivo.

Selective coexpression of multiple chemical markers defines discrete populations of neocortical GABAergic neurons.

Whether neocortical γ-aminobutyric acid (GABA) cells are composed of a limited number of distinct classes of neuron, or whether they are continuously differentiated with much higher diversity, remains a contentious issue for the field. Most GABA cells of rat frontal cortex have at least 1 of 6 chemical markers (parvalbumin, calretinin, alpha-actinin-2, somatostatin, vasoactive intestinal polypeptide, and cholecystokinin), with each chemical class comprising several distinct neuronal subtypes having specific physiological and morphological characteristics. To better clarify GABAergic neuron diversity, we assessed the colocalization of these 6 chemical markers with corticotropin-releasing factor (CRF), neuropeptide Y (NPY), the substance P receptor (SPR), and nitric oxide synthase (NOS); these 4 additional chemical markers suggested to be expressed diversely or specifically among cortical GABA cells. We further correlated morphological and physiological characteristics of identified some chemical subclasses of inhibitory neurons. Our results reveal expression specificity of CRF, NPY, SPR, and NOS in morphologically and physiologically distinct interneuron classes. These observations support the existence of a limited number of functionally distinct subtypes of GABA cells in the neocortex.

Substantia nigra output to prefrontal cortex via thalamus in monkeys. I. Electrophysiological identification of thalamic relay neurons.

A few studies have been performed in primate basal ganglia-thalamo-prefrontal pathways. Nevertheless, their electrophysiological properties and anatomical arrangements remain obscure. This study examined them in nigro-thalamo-cortical pathways from the substantia nigra pars reticulata (SNr) to the frontal cortex (FRC) via the mediodorsal (MD) and ventral anterior (VA) thalamus in monkeys. First, single thalamocortical neurons with SNr input were identified by antidromic responses to FRC stimulation and by inhibitory orthodromic responses with short latencies (<5 ms) to SNr stimulation. Second, single nigrothalamic neurons were found by antidromic responses to stimulation of the portions of the MD and VA where the thalamocortical neurons were recorded. The inhibitory orthodromic responses in the thalamocortical neurons were considered to be monosynaptically induced by nigral stimulation because the latency distribution of the orthodromic responses in the thalamocortical neurons was similar to that of the antidromic responses in the nigrothalamic neurons. Almost all relay neurons in the rostrolateral MD received inhibitory afferents from the caudolateral SNr and projected to the prefrontal area ventral to the principal sulcus, which constituted the densest nigro-thalamo-cortical projections. Meanwhile, neurons in the VA received inhibitory signals from the whole rostrocaudal extent of the SNr and projected to wide regions of the FRC; neurons in its pars magnocellularis mostly projected to different prefrontal areas, while those in its pars parvocellularis projected to motor areas. This report substantiated the topography of thalamocortical neurons monosynaptically receiving inhibitory SNr input and projecting to the FRC in the primate MD and VA at the single-neuron level.

Electrophysiological classification of somatostatin-positive interneurons in mouse sensorimotor cortex.

Classification of inhibitory interneurons is critical in determining their role in normal information processing and pathophysiological conditions such as epilepsy. Classification schemes have relied on morphological, physiological, biochemical, and molecular criteria; and clear correlations have been demonstrated between firing patterns and cellular markers such as neuropeptides and calcium-binding proteins. This molecular diversity has allowed generation of transgenic mouse strains in which GFP expression is linked to the expression of one of these markers and presumably a single subtype of neuron. In the GIN mouse (EGFP-expressing Inhibitory Neurons), a subpopulation of somatostatin-containing interneurons in the hippocampus and neocortex is labeled with enhanced green fluorescent protein (EGFP). To optimize the use of the GIN mouse, it is critical to know whether the population of somatostatin-EGFP-expressing interneurons is homogeneous. We performed unsupervised cluster analysis on 46 EGFP-expressing interneurons, based on data obtained from whole cell patch-clamp recordings. Cells were classified according to a number of electrophysiological variables related to spontaneous excitatory postsynaptic currents (sEPSCs), firing behavior, and intrinsic membrane properties. EGFP-expressing interneurons were heterogeneous and at least four subgroups could be distinguished. In addition, multiple discriminant analysis was applied to data collected during whole cell recordings to develop an algorithm for predicting the group membership of newly encountered EGFP-expressing interneurons. Our data are consistent with a heterogeneous population of neurons based on electrophysiological properties and indicate that EGFP expression in the GIN mouse is not restricted to a single class of somatostatin-positive interneuron.

Distinct subtypes of somatostatin-containing neocortical interneurons revealed in transgenic mice.

GABA-releasing inhibitory interneurons in the cerebral cortex can be classified by their neurochemical content, firing patterns, or axonal targets, to name the most common criteria, but whether classifications using different criteria converge on the same neuronal subtypes, and how many such subtypes exist, is a matter of much current interest and considerable debate. To address these issues, we generated transgenic mice expressing green fluorescent protein (GFP) under control of the GAD67 promoter. In two of these lines, named X94 and X98, GFP expression in the barrel cortex was restricted to subsets of somatostatin-containing (SOM+) GABAergic interneurons, similar to the previously reported "GIN" line (Oliva et al., 2000), but the laminar distributions of GFP-expressing (GFP+) cell bodies in the X94, X98, and GIN lines were distinct and nearly complementary. We compared neurochemical content and axonal distribution patterns of GFP+ neurons among the three lines and analyzed in detail electrophysiological properties in a dataset of 150 neurons recorded in whole-cell, current-clamp mode. By all criteria, there was nearly perfect segregation of X94 and X98 GFP+ neurons, whereas GIN GFP+ neurons exhibited intermediate properties. In the X98 line, GFP expression was found in infragranular, calbindin-containing, layer 1-targeting ("Martinotti") cells that had a propensity to fire low-threshold calcium spikes, whereas X94 GFP+ cells were stuttering interneurons with quasi fast-spiking properties, residing in and targeting the thalamo-recipient neocortical layers. We conclude that much of the variability previously attributed to neocortical SOM+ interneurons can be accounted for by their natural grouping into distinct subtypes.

Neurochemical diversity of neurogliaform cells in the human primary motor cortex.

Neurogliaform cells of area 4 of the human motor cortex were found to express choline acetyl transferase (ChAT), gamma-aminobutyric acid, and calbindin. GABA- and calbindin-positive NGCs were mainly localized in layers II and VI and were relatively rare in layer I of the cortex. ChAT-positive NGCs were observed in the upper and middle thirds of layer II, occurring occasionally in layer I and the upper portion of layer III. Their numbers were low compared to those of GABA- and calbindin-positive NGCs in layers II/III. The dendrites of ChAT-positive NGCs were short and few in number. Axonal arborizations of neighboring ChAT-positive cells interpenetrated considerably so that each ChAT-positive cell body was normally surrounded by axonal trees of the parent and a few other ChAT-positive NGCs. NGC axon collaterals surrounded small neuropil areas containing perikarya presumptive pyramidal neurons. The findings are discussed in the context of information processing in cortical modules and interaction of excitatory and inhibitory interneurons.

Barrel cortex microcircuits: thalamocortical feedforward inhibition in spiny stellate cells is mediated by a small number of fast-spiking interneurons.

Inhibitory and excitatory neurons located in rodent barrel cortex are known to form functional circuits mediating vibrissal sensation. Excitatory neurons located in a single barrel greatly outnumber interneurons, and form extensive reciprocal excitatory synaptic contacts. Inhibitory and excitatory networks must interact to shape information ascending to cortex. The details of these interactions, however, have not been completely explored. Using paired intracellular recordings, we studied the properties of synaptic connections between spiny neurons (i.e., spiny stellate and pyramidal cells) and interneurons, as well as integration of thalamocortical (TC) input, in layer IV barrels of rat thalamocortical slices. Results show the following: (1) the strength of unitary excitatory connections of spiny neurons is similar among different targets; (2) although inhibition from regular-spiking nonpyramidal interneurons to spiny neurons is comparable in strength to excitatory connections, inhibition mediated by fast-spiking (FS) interneurons is 10 times more powerful; (3) TC EPSPs elicit reliable and precisely timed action potentials in FS neurons; and (4) a small number of FS neurons mediate thalamocortical feedforward inhibition in each spiny neuron and can powerfully shunt TC-mediated excitation. The ready activation of FS cells by TC inputs, coupled with powerful feedforward inhibition from these neurons, would profoundly influence sensory processing and constrain runaway excitation in vivo.

Medial olivocochlear reflex interneurons are located in the posteroventral cochlear nucleus: a kainic acid lesion study in guinea pigs.

The medial olivocochlear (MOC) reflex arc is probably a three-neuron pathway consisting of type I spiral ganglion neurons, reflex interneurons in the cochlear nucleus, and MOC neurons that project to the outer hair cells of the cochlea. We investigated the identity of MOC reflex interneurons in the cochlear nucleus by assaying their regional distribution using focal injections of kainic acid. Our reflex metric was the amount of change in the distortion product otoacoustic emission (at 2f(1)-f(2)) just after onset of the primary tones. This metric for MOC reflex strength has been shown to depend on an intact reflex pathway. Lesions involving the posteroventral cochlear nucleus (PVCN), but not the other subdivisions, produced long-term decreases in MOC reflex strength. The degree of cell loss within the dorsal part of the PVCN was a predictor of whether the lesion affected MOC reflex strength. We suggest that multipolar cells within the PVCN have the distribution and response characteristics appropriate to be the MOC reflex interneurons.

Interlaminar connections in the neocortex.

This review summarizes the local circuit, interlaminar connections in adult mammalian neocortex. These were first demonstrated with anatomical techniques, which indicate some of the exquisite spatial precision present in the circuitry. Details, such as the class(es) of neurons targeted by some of these projections, have begun to be added in studies that combine paired/triple intracellular recordings with dye-filling of connected neurons. Clear patterns are emerging from these studies, with 'forward' projections from layer 4 to 3 and from 3 to 5 targeting both selected pyramidal cells and interneurons, while 'back' projections from layer 5 to 3 and from 3 to 4 target only interneurons. To place these data in a wider context, the major afferent inputs to and efferent outputs from each of the layers are discussed first.

Fast-spike interneurons and feedforward inhibition in awake sensory neocortex.

'Fast-spike' interneurons of layer 4 mediate thalamocortical feedforward inhibition and can, with some confidence, be identified using extracellular methods. In somatosensory barrel cortex of awake rabbits, these 'suspected inhibitory interneurons' (SINs) have distinct receptive field properties: they respond to vibrissa displacement with very high sensitivity and temporal fidelity. However, they lack the directional specificity that is clearly seen in most of their ventrobasal thalamocortical afferents. Several lines of evidence show that layer-4 SINs receive a potent and highly convergent and divergent functional input from topographically aligned thalamocortical neurons. Whereas the unselective pooling of convergent thalamocortical inputs onto SINs generates sensitive and broadly tuned inhibitory receptive fields, the potent divergence of single thalamocortical neurons onto many SINs generates sharply synchronous (+/-1 ms) activity (because of coincident EPSPs). Synchronous discharge of these interneurons following thalamocortical impulses will generate a synchronous feedforward release of GABA within the barrel. Thalamocortical impulses will, therefore, generate only a brief 'window of excitability' during which spikes can occur in the post-synaptic targets of fast-spike interneurons. This fast, synchronous, highly sensitive and broadly tuned feed-forward inhibitory network is well suited to suppress spike generation in spiny neurons following all but the most optimal feedforward excitatory inputs.

Understanding layer 4 of the cortical circuit: a model based on cat V1.

This paper reviews theoretical and experimental results on the processing of layer 4, the input-recipient layer, of cat primary visual cortex (V1). A wide range of experimental data can be understood from a model in which response tuning of layer 4 cells is largely determined by a local interplay of feedforward excitation (from thalamus) and feedforward inhibition (from layer 4 inhibitory interneurons driven by thalamus). Feedforward inhibition dominates excitation, inherits its tuning from the thalamic input and sharpens the tuning of excitatory cells. At least a strong component of the feedforward inhibition received by a cell is spatially opponent to the excitation it receives, meaning that inhibition is driven by dark in regions of the visual field in which excitation is driven by light, and vice versa. The idea of opponent inhibition can be generalized to mean inhibition driven by input patterns that are strongly anti-correlated with the patterns that excite a cell. This paper argues that dominant feedforward opponent inhibition may be a general principle of cortical layer 4. This leads to the suggestion that the properties that show columnar organization--invariance across the vertical depth of cortex--may be properties that are shared by 'opposite' (anticorrelated) stimulus pairs. This contrasts with the more common idea that a column represents a set of cells that all share similar stimulus preferences.

Columnar transformations in auditory cortex? A comparison to visual and somatosensory cortices.

Auditory cortical columns have been studied for decades, but intracolumnar processing in auditory cortex is still poorly understood, relative to what is known about such processing in visual cortex and somatosensory cortex. While there are certainly striking similarities in cortical structure across the modalities, investigations of auditory cortex anatomy and synaptic physiology have also found important differences from the columnar organization of other sensory cortices. In vitro and in vivo studies of thalamocortical transformations in the auditory system have begun to reveal the functional significance of these differences, and have defined the earliest stages of auditory cortical processing. However, the question of what transformations are performed within auditory cortical columns remains unresolved. Attempts to find laminar differences in auditory cortex, which could provide the key to understanding columnar transformations, have so far produced contradictory and inconclusive results. Direct analogies to primary visual and somatic sensory cortices would suggest that response properties such as bandwidth, inhibitory sideband structure, preferred modulation rate and modulation phase sensitivity might vary across layers in auditory cortex. While such analogies could prove useful as guidelines for future research, the best hope for understanding auditory columnar transformations may lie instead with a more modality-specific, functional approach.

Thalamocortical bursts trigger recurrent activity in neocortical networks: layer 4 as a frequency-dependent gate.

Sensory information reaches the cortex via thalamocortical (TC) synapses in layer 4. Thalamic relay neurons that mediate information flow to cortex operate in two distinct modes, tonic and burst firing. Burst firing has been implicated in enhancing reliability of information flow between individual neurons. However, little is known about how local networks of neocortical neurons respond to different temporal patterns of TC activity. We studied cortical activity patterns evoked by stimulating TC afferents at different frequencies, using a combination of electrophysiology and calcium imaging in TC slices that allowed for the reconstruction of spatiotemporal activity with single-cell resolution. Stimulation of TC axons at low frequencies triggered action potentials in only a small number of layer 4 neurons. In contrast, brief high-frequency stimulus trains triggered widespread recurrent activity in populations of neurons in layer 4 and then spread into adjacent layers 2/3 and 5. Recurrent activity had a clear threshold, typically lasted 300 msec, and could be evoked repetitively at frequencies up to 0.5 Hz. Moreover, the spatial extent of recurrent activity was controlled by the TC pattern of activity. Recurrent activity triggered within the highly interconnected networks of layer 4 might act to selectively amplify and redistribute transient high-frequency TC inputs, filter out low-frequency inputs, and temporarily preserve a record of past sensory activity.

Parvalbumin, somatostatin and cholecystokinin as chemical markers for specific GABAergic interneuron types in the rat frontal cortex.

It remains to be clarified how many classes of GABAergic nonpyramidal cells exist in the cortical circuit. We have divided GABA cells in the rat frontal cortex into 3 groups, based on their firing characteristics: fast-spiking (FS) cells, late-spiking (LS) cells, and non-FS cells. Expression of calcium-binding proteins and peptides could be shown in separate groups of GABA cells in layers II/III and V of the frontal cortex: (1) parvalbumin cells, (2) somatostatin cells, (3) calretinin and/or vasoactive intestinal polypeptide (VIP) cells [partially positive for cholecystokinin (CCK)] and (4) large CCK cells (almost negative for VIP/calretinin). Combining the physiological and chemical properties of morphologically diverse nonpyramidal cells allows division into several groups, including FS basket cells containing parvalbumin, non-FS somatostatin Martinotti cells with ascending axonal arbors, and non-FS large basket cells positive for CCK. These subtypes show characteristic spatial distributions of axon collaterals and the innervation tendency of postsynaptic elements. With synchronized activity induced by cortical excitatory or inhibitory circuits, firing patterns were also found to differ. Subtype-selective occurrence of electrical coupling, finding for potassium channel Kv3.1 proteins, and cholinergic and serotonergic modulation supports our tentative classification. To clarify the functional architecture in the frontal cortex, it is important to reveal the connectional characteristics of GABA cell subtypes and determine whether they are similar to those in other cortical regions.

Diverse types of interneurons generate thalamus-evoked feedforward inhibition in the mouse barrel cortex.

Sensory information, relayed through the thalamus, arrives in the neocortex as excitatory input, but rapidly induces strong disynaptic inhibition that constrains the cortical flow of excitation both spatially and temporally. This feedforward inhibition is generated by intracortical interneurons whose precise identity and properties were not known. To characterize interneurons generating feedforward inhibition, neurons in layers IV and V of mouse somatosensory ("barrel") cortex in vitro were tested in the cell-attached configuration for thalamocortically induced firing and in the whole-cell mode for synaptic responses. Identification as inhibitory or excitatory neurons was based on intrinsic firing patterns and on morphology revealed by intracellular staining. Thalamocortical stimulation evoked action potentials in approximately 60% of inhibitory interneurons but in <5% of excitatory neurons. The inhibitory interneurons that fired received fivefold larger thalamocortical inputs compared with nonfiring inhibitory or excitatory neurons. Thalamocortically evoked spikes in inhibitory interneurons followed at short latency the onset of excitatory monosynaptic responses in the same cells and slightly preceded the onset of inhibitory responses in nearby neurons, indicating their involvement in disynaptic inhibition. Both nonadapting (fast-spiking) and adapting (regular-spiking) inhibitory interneurons fired on thalamocortical stimulation, as did interneurons expressing parvalbumin, calbindin, or neither calcium-binding protein. Morphological analysis revealed that some interneurons might generate feedforward inhibition within their own layer IV barrel, whereas others may convey inhibition to upper layers, within their own or in adjacent columns. We conclude that feedforward inhibition is generated by diverse classes of interneurons, possibly serving different roles in the processing of incoming sensory information.

Two distinct subgroups of cholecystokinin-immunoreactive cortical interneurons.

Examination of cholecystokinin-immunoreactive cells in the rat frontal cortex revealed the presence in layers I-VI of a non-uniform population ranging in size from small to large. All were also immunoreactive for GABA. The most commonly observed dendritic form of the small cells were bipolar or bitufted although some were multipolar and demonstrated vasoactive intestinal polypeptide and in a few case calretinin immunoreactivity. The large cells were multipolar or bitufted and lacked expression of vasoactive intestinal polypeptide and calretinin immunoreactivity but occasionally showed calbindin D28k immunoreactivity. Therefore, the cholecystokinin-immunoreactive cells could be divided into two distinct subpopulations depending on their chemistry and morphology. Our previous studies showed that GABAergic cells in the neocortex could be classified into at least three chemically different subgroups: (1) parvalbumin-containing cells; (2) somatostatin-containing cells (most of them also contain calbindin D28k); and (3) vasoactive intestinal polypeptide- and/or calretinin-containing cells. The present results indicated that the small cholecystokinin-immunoreactive non-pyramidal cells constitute a subset of the vasoactive intestinal polypeptide- and/or calretinin-containing cortical GABAergic cells. The large cells remain to be categorized.

Role of central interneurons in habituation of swimming activity in the medicinal leech.

Swimming activity evoked by light tactile stimulation of a body wall flap in dissected leech preparations undergoes habituation (5). In this study, we examine the activity of several interneurons (cell 204, cell 205, the S cell, and cell 208) during habituation trials to study further the neuronal mechanisms that mediate this decline in responsiveness. Light tactile stimulation of the leech body wall evoked initially a marked excitatory response in cell 204 homologs (segmental swim-initiating neurons) that preceded the initiation of swimming activity. This response decreased over the course of repeated stimulus trials; however, no marked decline in cell 204 activity accompanied the cessation of swim initiation. A similar activity pattern was observed in cell 205. Thus the habituation of swimming activity to stroking of the body wall is not due solely to reduced input to cell 204 and cell 205. The early activity of cell 204 was not correlated to the duration of subsequent swim episodes. However, the impulse frequency of cell 204 during swim episodes was negatively correlated to the period of swim cycles. This correlation between cell 204 activity and cycle period occurred both within individual episodes as well as between trials in a habituation series. Direct stimulation of cell 204 with current pulses evoked swimming activity reliably for an average of 72 trials. Therefore, habituation that results from stroking the body wall (which occurs after approximately 6 trials) is not mediated by plasticity in the connections between cell 204 and the swim oscillator. The S cell fired repeatedly in response to light tactile stimulation. This response declined with repeated trials. Intense intracellular stimulation of the S cell was sufficient to initiate swimming activity in some preparations. The magnitude and duration of the excitation required to initiate swimming by this means were far greater, however, than that which occurred during stroking the body wall. The response of cell 208 (a swim oscillator cell) to body wall stimulation during habituation trials was variable; usually an initial hyperpolarization was followed by some depolarization. No aspect of this response correlated with the onset of habituation. Our results are consistent with the idea that cell 204 and cell 205 are part of the pathway that mediates swimming activity in response to light tactile stimulation of the leech body wall, and that habituation occurs, in part, as the result of reduced sensory input to this cell.(ABSTRACT TRUNCATED AT 400 WORDS)

A correlative electron microscopic study of basket cells and large GABAergic neurons in the monkey sensory-motor cortex.

Large basket cells were identified in Golgi and horseradish peroxidase labeled material from the sensory-motor cortex of adult monkeys. Their morphology was correlated at the light and electron microscopic level with large comparable cells stained immunocytochemically for glutamate decarboxylase. In Golgi-impregnated material these cells have a very large cell body and dendrites that extend through several layers of the cortex with a predominant vertical orientation. The axon is only stained for a few micrometers. The same cells studied electron microscopically in serial sections after gold-toning show very distinctive ultrastructural characteristics: the cell bodies contain a large number of organelles, the nuclei are rounded with homogeneously dispersed chromatin and synapsing onto the somata are many axon terminals, both symmetrical and asymmetrical but the symmetrical type forms 70-80% of the total; dendrites also receive a large number of both symmetrical and asymmetrical synaptic contacts. All the axons of basket cells become myelinated and the Golgi labeling of the initial segments is interrupted at the commencement of the first myelin internode. The axon initial segments receive several symmetrical synaptic contacts in the proximal one-third of their length. The axonal arborization of a basket cell retrogradely labeled in the somatosensory cortex after intracortical injection of horseradish peroxidase was analyzed in detail. The mainly horizontal axonal collaterals of this cell are myelinated for most of their trajectory and have a preferred orientation in the anteroposterior dimension. These axonal collaterals, although very long (more than 1.8 mm), at intervals give rise to a small number of short unmyelinated terminal branches that bear a series of boutons terminaux forming a multi-terminal ending. The multi-terminal endings surround somata and proximal dendrites of pyramidal and non-pyramidal cells. Dense pericellular terminations (baskets or nests) like those drawn by Ramón y Cajal and Marin-Padilla are not formed by the axon of a single basket cell. Thus, basket formations are presumably formed by converging axons from several basket cells. Immunocytochemical material was stained for glutamate decarboxylase, the enzyme involved in the synthesis of gamma-aminobutyrate (GABA). This shows that large glutamate decarboxylase-positive neurons of the same size as those positively identified as basket cells in the Golgi and horseradish peroxidase material have virtually the same morphological characteristics, at both the light and electron microscope levels, as the basket cells.(ABSTRACT TRUNCATED AT 400 WORDS)