Specificity of cortical synaptic connectivity: emphasis on perspectives gained from quantitative electron microscopy

This report traces the historical development of concepts regarding the specificity of synaptic connectivity in the cerebral cortex as viewed primarily from the perspective of electron microscopy. The occurrence of stereotypical patterns of connection (e.g., contrasting synaptic patterns on the surfaces of spiny vs. non-spiny neurons, the general consistency with which axonal pathways impinge on and originate within specific cortical areas and layers, triadic synaptic relationships) implies that cortical connectivity is highly structured. The high degree of order characterizing many aspects of cortical organization is mirrored by an equally ordered arrangement of synaptic connections between specific types of neurons. This observation is based on quantitative electron microscopic studies of synapses between identified neurons and from the results of correlative anatomical/electrophysiological investigations. The recognition of recurring synaptic patterns and responses between specific neurons has generated increased support for the notion of specificity of synaptic connections at the expense of randomness, but the role of specificity in cortical function is an unresolved question. At the core of cortical processing lie myriad possibilities for computation provided by the wealth of synaptic connections involving each cortical neuron. Specificity, by limiting possibilities for connection, can impose an order on synaptic interactions even as processes of dynamic selection or synaptic remodeling ensure the constant formation and dissolution of cortical circuits. These operations make maximal use of the richness of cortical synaptic connections to produce a highly flexible system, irrespective of the degree of randomness or specificity that obtains for cortical wiring at any particular time.     

Interactions between cat striate cortex neurons

A series of simultaneous recordings from several striate cortex neurons were made in paralyzed, anesthetized cats. Recordings were obtained with one or two bundles of extra fine wires and originated from one and two cortical orientation columns. Standard PST histograms and, in some cases, response planes were used to analyse the neuronal receptive fields. Functional connectivity between neurons was assessed by cross-correlation of their spike trains. It was found that 61% of neuronal pairs found within a column shared the same input, either excitatory or inhibitory, Even if neurons in a pair belonged to two different columns separated by 1mm lateral distance, 40% of pairs still exhibited shared input coordination. This type of coordination could also encompass all combinations of simple and complex fields in the pair. Direct connections between neurons were found almost exclusively within columns: excitatory connections were found in 20% of cases and inhibitory in 8%. Direct connections were often accompanied by the other types of interactions. Only one example of excitatory and one of inhibitory direct connections were found between columns. In both cases preferred orientations were almost identical.     

Cross-correlation analysis of a recurrent inhibitory circuit in the rat thalamus

Spontaneous activities of vibrissa-responding neurons in the rat ventrobasal complex (VB) and somatosensory part of the thalamic reticular nucleus (S-TR) were simultaneously recorded and subjected to cross-correlation analysis to investigate the functional organization of recurrent inhibitory action of the S-TR on VB neurons. Excitatory and/or inhibitory interactions were found between approximately 75% (25/34) of the pairs of S-TR and VB neurons with receptive fields (RFs) on the same vibrissa. In contrast, there was no significant interaction between 54 pairs of neurons having RFs on different vibrissae. Among the pairs of neurons with RFs on the same vibrissa, there were four types of correlations, which indicate the following connections: monosynaptic excitation from a VB to an S-TR neuron (7 pairs), monosynaptic inhibition from an S-TR to a VB neuron (10 pairs), reciprocal connection combining the above two types (7 pairs), and common excitation in addition to inhibition from an S-TR to a VB neuron (1 pair). Examples of divergence and convergence of connections between S-TR and VB neurons were demonstrated by testing one S-TR (VB) neuron with more than one VB (S-TR) neuron. Vibrissa-suppressed VB cells, which had exclusively inhibitory RFs, were included in eight pairs of the above samples. These VB cells were more likely to receive inhibitory inputs from S-TR neurons than other VB neurons. Cells with RFs on multiple vibrissae were included in the other 10 pairs. These multiple-vibrissa cells had no interaction with single-vibrissa cells but did with multiple-vibrissa cells. From the incidence of four types of correlation between S-TR and VB neurons with RFs on the same vibrissa, the following connection pattern is suggested: One S-TR neuron receives excitatory inputs from approximately 40% of the VB neurons with RFs on the same vibrissa and sends inhibitory outputs to approximately 55%. Since these two groups of VB neurons were overlapping, the S-TR neuron has reciprocal connections with approximately 20% of the VB neurons with RFs on the same vibrissa. The same estimate was applied to connectivity of one VB neuron. These results indicate that both inputs and outputs of S-TR neurons are precisely and topographically organized, although there is convergence to and divergence from a substantial number of VB neurons with RFs on the same vibrissa. It is proposed that the recurrent inhibitory circuit through the S-TR plays a role in improving discrimination of sensory information transmitted through the VB.     

Somatosensory response properties of excitatory and inhibitory neurons in rat motor cortex

In sensory cortical networks, peripheral inputs differentially activate excitatory and inhibitory neurons. Inhibitory neurons typically have larger responses and broader receptive field tuning compared with excitatory neurons. These differences are thought to underlie the powerful feedforward inhibition that occurs in response to sensory input. In the motor cortex, as in the somatosensory cortex, cutaneous and proprioceptive somatosensory inputs, generated before and during movement, strongly and dynamically modulate the activity of motor neurons involved in a movement and ultimately shape cortical command. Human studies suggest that somatosensory inputs modulate motor cortical activity in a center excitation, surround inhibition manner such that input from the activated muscle excites motor cortical neurons that project to it, whereas somatosensory input from nearby, nonactivated muscles inhibit these neurons. A key prediction of this hypothesis is that inhibitory and excitatory motor cortical neurons respond differently to somatosensory inputs. We tested this prediction with the use of multisite extracellular recordings in anesthetized rats. We found that fast-spiking (presumably inhibitory) neurons respond to tactile and proprioceptive inputs at shorter latencies and larger response magnitudes compared with regular-spiking (presumably excitatory) neurons. In contrast, we found no differences in the receptive field size of these neuronal populations. Strikingly, all fast-spiking neuron pairs analyzed with cross-correlation analysis displayed common excitation, which was significantly more prevalent than common excitation for regular-spiking neuron pairs. These findings suggest that somatosensory inputs preferentially evoke feedforward inhibition in the motor cortex. We suggest that this provides a mechanism for dynamic selection of motor cortical modules during voluntary movements.     

Delayed excitatory connections in the flight system of the locust

1. Synaptic interactions between identified neurons in the flight system of the locust were investigated by the use of standard intracellular recording and staining techniques. The intent was to determine the distribution and functional significance of delayed excitatory connections, which have been previously described. 2. For one inhibitory connection it was demonstrated that subthreshold depolarization of the presynaptic neuron was sufficient to cause release of transmitter at the synapse. This established the existence of graded interactions between spiking flight neurons. 3. Three inhibitory interneurons were found to cause delayed excitatory responses in several other neurons. Often these were coupled with direct inhibitory connections between the same pre- and postsynaptic neurons, resulting in an inhibitory/excitatory (I/E) postsynaptic potential (PSP). The two phases of this PSP were variable. 4. Delayed excitatory connections appeared powerful while the flight system was inactive. However, these connections were disabled during flight rhythms at the phase when the presynaptic neuron was depolarized and firing action potentials. This was likely to be due to the nature of the disynaptic disinhibitory interaction being via (an) intervening neuron(s) with oscillating membrane potentials and thresholds for release of transmitter. 5. Thus connections demonstrated when flight rhythms were not expressed changed their character during flight rhythms. The delayed excitatory connections in this system probably reflect complex circuits of inhibition mediated by graded interactions and have little functional significance as phenomena in their own right.     

Correlation analysis of respiratory neuron activity in ventrolateral medulla of brainstem-spinal cord preparation isolated from newborn rat

Cross correlation analysis was used to study functional connections between one inspiratory (I) neuron and another, and between one preinspiratory (Pre-I) neuron and another, in 54 brainstemspinal cord preparations isolated from newborn rats. Pre-I neurons usually fired in the pre and post inspiratory phases. Neurons were recorded extracellularly with pairs of microelectrodes placed on the same or opposite sides of the brainstem. Fourteen pairs of Pre-I neurons recorded bilaterally in the rostral ventrolateral medulla (RVL), 14 pairs of ipsilateral Pre-I neurons in the RVL, 14 pairs of bilateral I neurons in the RVL and 12 pairs of ipsilateral I neurons in the ventrolateral medulla were studied. Cross correlation histograms (CCHs) were computed. Significantly high peak bin counts were detected in 24 of 54 pairs. Peaks on one side of the origin of the CCHs were observed for one pair of ipsilateral Pre-I neurons, four pairs of bilateral I neurons and five pairs of ipsilateral I neurons. These findings suggest mono or oligo synaptic excitatory connections between paired neurons or shared inputs. Only one trough suggesting an oligo-synaptic inhibitory connection was evident in a CCH obtained from the pair of bilateral I neurons. This CCH revealed the peak and the trough on opposite sides of the origin, which was consistent with reciprocal excitatory and inhibitory connections between recorded neurons. Peaks on both sides of the origin were observed for three pairs of bilateral I neurons. From autocorrelation analysis and the latencies of these peaks, two of the three CCHs were consistent with reciprocal excitatory connections between recorded neurons, whereas the other CCH suggests shared inputs. Peaks at the origin were observed for two pairs of ipsilateral Pre-I neurons, four pairs of bilateral I neurons and five pairs of ipsilateral I neurons. These results suggest shared inputs. For Pre-I neurons recorded in opposite sides, no significant bin counts were detected. Peaks on one side were detected for three pairs. Present results suggest short term synchronisation of I neurons, and of Pre-I neurons via excitatory coupling, and the likelihood of comparatively strong interaction between I neurons, which may be important in maintaining the I burst.     

Optimal sizes of dendritic and axonal arbors in a topographic projection

I consider a topographic projection between two neuronal layers with different densities of neurons. Given the number of output neurons connected to each input neuron (divergence) and the number of input neurons synapsing on each output neuron (convergence), I determine the widths of axonal and dendritic arbors which minimize the total volume of axons and dendrites. Analytical results for one-dimensional and two-dimensional projections can be summarized qualitatively in the following rule: neurons of the sparser layer should have arbors wider than those of the denser layer. This agrees with the anatomic data for retinal, cerebellar, olfactory bulb, and neocortical neurons the morphology and connectivity of which are known. The rule may be used to infer connectivity of neurons from their morphology.     

Quantification of the factors that influence discharge correlation in model motor neurons

The purpose of this study was to quantify the influence of intrinsic properties, active dendritic conductances, and background excitation and inhibition on measures of discharge correlation in the time and frequency domains with known levels and patterns of common synaptic input. The study involved a computer simulation of a population of neurons with a range of input resistances (0.54-3.7 MOmega) and surface areas (407,000-712,000 microm(2)). The neurons were simulated with no, moderate, or high levels of active dendritic conductances and were activated with either excitatory input only or excitatory and inhibitory inputs. The patterns of common input, either branched common input or common modulation, were tested with 0, 30, 60, and 90% common input. The results confirm previous findings of an exponential relation between the level of common input and indexes of synchronization; only when the common input comprised >/=60% of the total excitatory input was there a significant effect on discharge correlation. Synchronization was greatest in models that had passive dendrites. Active dendritic conductances caused the discharge rate of the neuron to saturate and decreased motor-unit synchronization. However, the addition of 10% background inhibitory input increased synchronization in these models. In contrast, common rhythmic modulation of inputs at 24 Hz usually decreased synchronization. Significant coherence at the modulated frequency occurred in the commonly modulated neurons when >/=60% of the inputs were modulated. Furthermore, active dendritic conductances decreased coherence. Branched common input caused high levels of coherence across a broad spectrum and when combined with active dendritic conductances caused significant frequency peaks in the 30- to 50-Hz band. In conclusion, the level of inhibitory input and active dendritic conductances interact with the amount of common input to determine time- and frequency-domain discharge correlation.     

Synaptic connections between nonspiking afferent neurons and motor neurons underlying phase-dependent reflexes in crayfish.

1. This paper analyzes the synaptic connections made by nonspiking afferent neurons of the thoracocoxal muscle receptor organ (TCMRO) with basal limb motor neurons in the crayfish. The T fiber, a dynamically sensitive afferent, monosynaptically excites promotor motor neurons. Evidence suggests that both tonic graded chemical transmission and electrical synaptic transmission may be involved, depending on the motor neuron under consideration. 2. In preparations in the active state (spontaneously producing reciprocal motor patterns), the T fiber also inhibits promotor motor neurons in a phase-dependent manner. This inhibitory pathway is probably indirect, because it involves additional synaptic delay. 3. The statically sensitive S fiber also excites promotor motor neurons, but phase-dependent inhibition of promotor motor neurons by the S fiber was not seen. 4. The T fiber excites a subclass of remotor motor neurons (group 1) by a combination of direct chemical input and electrical input. This connection underlies the positive feedback reflex that excites these remotor motor neurons, in a phase-dependent manner, on stretch of the TCMRO during the active state. In inactive preparations, this connection remains subthreshold. 5. Central synaptic outputs of group 1 remotor motor neurons can also inhibit promotor motor neurons. This pathway may contribute to the phase-dependent reflex inhibition of promotor motor neurons that occurs in the active state.     

Examining neocortical circuits: some background and facts

The first definitive studies of where afferents to cerebral cortex terminate were made possible by the finding that as they degenerate axon terminals become electron dense. Gold toning of Golgi impregnated neurons allowed the postsynaptic targets of these afferents to be identified by electron microscopy and also allowed the termination sites of axons from a variety of types of cortical neurons to be ascertained, while the development of antibodies to GAD and to GABA made it possible to determine which types of cortical neurons are inhibitory. Subsequently the use of gold toned, Golgi impregnated material to examine neuronal connectivity was made redundant by the development of techniques that allowed the physiological properties of cortical neurons to be evaluated in neurons filled intracellularly with markers. Intracellular filling showed the axonal trees of cortical neurons are much more widespread than had been revealed by Golgi impregnations. As a result of numerous studies of the axons of identified neurons, we know a great deal about where most of the different types of neurons in cerebral cortex form their synapses, but on the other side of the picture there is a dearth of information about the origins of the inputs that specific types of cortical neurons receive. However, it is evident that each cortical neuron is the focus of input from many other neurons, and on the basis of the available data it is estimated that a single pyramidal cell in cortex receives its input from as many as 1,000 other excitatory neurons and as many as 75 inhibitory neurons.     

A modeler's view on the spatial structure of intrinsic horizontal connectivity in the neocortex

Most current computational models of neocortical networks assume a homogeneous and isotropic arrangement of local synaptic couplings between neurons. Sparse, recurrent connectivity is typically implemented with simple statistical wiring rules. For spatially extended networks, however, such random graph models are inadequate because they ignore the traits of neuron geometry, most notably various distance dependent features of horizontal connectivity. It is to be expected that such non-random structural attributes have a great impact, both on the spatio-temporal activity dynamics and on the biological function of neocortical networks. Here we review the neuroanatomical literature describing long-range horizontal connectivity in the neocortex over distances of up to eight millimeters, in various cortical areas and mammalian species. We extract the main common features from these data to allow for improved models of large-scale cortical networks. Such models include, next to short-range neighborhood coupling, also long-range patchy connections.     

Laminar sources of synaptic input to cortical inhibitory interneurons and pyramidal neurons

The functional role of an individual neuron within a cortical circuit is largely determined by that neuron's synaptic input. We examined the laminar sources of local input to subtypes of cortical neurons in layer 2/3 of rat visual cortex using laser scanning photostimulation. We identified three distinct laminar patterns of excitatory input that correspond to physiological and morphological subtypes of neurons. Fast-spiking inhibitory basket cells and excitatory pyramidal neurons received strong excitatory input from middle cortical layers. In contrast, adapting inhibitory interneurons received their strongest excitatory input either from deep layers or laterally from within layer 2/3. Thus, differential laminar sources of excitatory inputs contribute to the functional diversity of cortical inhibitory interneurons.     

Descending corticofugal neurons in layer 5 of rabbit S1: evidence for potent corticocortical, but not thalamocortical, input

Extracellular recordings were obtained from descending corticofugal neurons of layer 5 (CF-5 neurons) in primary somatosensory cortex (S1) of awake rabbits. These cells were identified by antidromic activation via stimulation sites in ventrobasal (VB) thalamus. Recordings were also obtained from putative GABAergic interneurons (suspected inhibitory interneurons, SINs) located in the same microelectrode penetrations, and in close proximity (±300 μm) to the CF-5 neurons. In some experiments, the above populations were recorded simultaneously with neurons in the topographically aligned VB thalamic barreloid. Each of several experimental strategies failed to reveal evidence of monosynaptic thalamic input to CF-5 neurons, but revealed a clear monosynaptic input to neighboring SINs: (1) whereas CF-5 neurons responded at very long synaptic latencies to intense electrical stimulation of VB thalamus, neighboring SINs responded at short latencies; (2) whereas cross-correlations between CF-5 neurons and topographically aligned VB neurons failed to show significant peaks indicative of monosynaptic VB input, neighboring SINs did show such peaks; and (3) whereas CF-5 neurons were unresponsive to microstimulation of topographically aligned VB thalamic barreloids, neighboring SINs were very responsive to such stimulation. Both CF-5 neurons and neighboring SINs responded to electrical stimulation of the corpus callosum with a robust, short-latency synaptic response. This finding demonstrates that CF-5 neurons are capable of vigorous, short-latency responses to excitatory synaptic input. These data suggest considerable specificity in the thalamocortical connectivity of subpopulations within layer 5, and support the notion that CF-5 neurons are dominated by corticocortical rather than thalamocortical input. Received: 4 January 1999 / Accepted: 12 July 1999     

Contrasting of synaptic signals by simultaneous modification of excitatory and inhibitory inputs

Conditions facilitating long-term contrasting of interneuronal connections were studied using a mathematical model of posttetanic Ca²⁺-dependent postsynaptic processes in pyramidal neurons of hippocampal field CA₃. These studies demonstrated that modified inhibition selectively facilitates long-term potentiation of the efficiency of one of the interneuronal connections when the presynaptic neuron discharges at a given frequency for a short time, while connections formed from the same postsynaptic cell with other presynaptic neurons undergo long-term depression. The mechanism underlying this contrasting may involve long-term depression of the efficiency of disynaptic inhibitory transmission to the rhythmically stimulated input, even when the efficiency of monosynaptic excitatory transmission at the same input is low and undergoes minimal potentiation. When the “common” inhibitory neuron is simultaneously activated by various presynaptic cells, heterosynaptic potentiation of inhibitory transmission can simultaneously develop at the other inputs of the postsynaptic cell, without change in the efficiency of excitatory transmission, which leads to long-term depression of the efficiency of the connections between other excitatory neurons and the postsynaptic cell. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 46, No. 6, pp. 1076–1087, November–December, 1996.     

Graded synaptic interactions between local premotor interneurons of the locust.

1. Graded synaptic interactions are revealed between pairs of nonspiking, local interneurons in the metathroracic ganglion of the locust. These interneurons drive motor neurons innervating muscles of a hindleg. 2. All the interactions found between the interneurons are inhibitory and one way. Synaptic transmission is effected by the graded release of chemical transmitter. Some of the connections are apparently direct. One local interneuron can, therefore, exert a graded control over the membrane potential of another local interneuron. 3. There are inhibitory connections between local interneurons that excite the same motor neuron, between local interneurons that excite antagonistic motor neurons, and between local interneurons that excite motor neurons to muscles moving different joints of a hindleg. 4. Other pairs of interneurons, which are not connected, may be driven by common synaptic inputs. Their outputs add together at the level of the motor neurons to produce effects that are greater than the sum of their individual effects. 5. It is proposed that graded interactions between these local interneurons are an essential element in the generation of motor patterns.     

Inhibitory interactions between spiny projection neurons in the rat striatum

The spiny projection neurons are by far the most numerous type of striatal neuron. In addition to being the principal projection neurons of the striatum, the spiny projection neurons also have an extensive network of local axon collaterals by which they make synaptic connections with other striatal projection neurons. However, up to now there has been no direct physiological evidence for functional inhibitory interactions between spiny projection neurons. Here we present new evidence that striatal projection neurons are interconnected by functional inhibitory synapses. To examine the physiological properties of unitary inhibitory postsynaptic potentials (IPSPs), dual intracellular recordings were made from pairs of spiny projection neurons in brain slices of adult rat striatum. Synaptic interactions were found in 9 of 45 pairs of neurons using averages of 200 traces that were triggered by a single presynaptic action potential. In all cases, synaptic interactions were unidirectional, and no bidirectional interactions were detected. Unitary IPSPs evoked by a single presynaptic action potential had a peak amplitude ranging from 157 to 319 microV in different connections (mean: 277 +/- 46 microV, n = 9). The percentage of failures of single action potentials to evoke a unitary IPSP was estimated and ranged from 9 to 63% (mean: 38 +/- 14%, n = 9). Unitary IPSPs were reversibly blocked by bicuculline (n = 4) and had a reversal potential of -62.4 +/- 0.7 mV (n = 5), consistent with GABA-mediated inhibition. The findings of the present study correlate very well with anatomical evidence for local synaptic connectivity between spiny projection neurons and suggest that lateral inhibition plays a significant role in the information processing operations of the striatum.     

Primary visual cortex shows laminar‐specific and balanced circuit organization of excitatory and inhibitory synaptic connectivity

Key points

• Using functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory neurons in layers 2/3–6 of the mouse visual cortex (V1).
• Laminar‐specific synaptic wiring diagrams of excitatory neurons were constructed on the basis of circuit mapping.
• The present study reveals that that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks in V1.

Abstract

In the mammalian neocortex, excitatory neurons provide excitation in both columnar and laminar dimensions, which is modulated further by inhibitory neurons. However, our understanding of intracortical excitatory and inhibitory synaptic inputs in relation to principal excitatory neurons remains incomplete, and it is unclear how local excitatory and inhibitory synaptic connections to excitatory neurons are spatially organized on a layer‐by‐layer basis. In the present study, we combined whole cell recordings with laser scanning photostimulation via glutamate uncaging to map excitatory and inhibitory synaptic inputs to single excitatory neurons throughout cortical layers 2/3–6 in the mouse primary visual cortex (V1). We find that synaptic input sources of excitatory neurons span the radial columns of laminar microcircuits, and excitatory neurons in different V1 laminae exhibit distinct patterns of layer‐specific organization of excitatory inputs. Remarkably, the spatial extent of inhibitory inputs of excitatory neurons for a given layer closely mirrors that of their excitatory input sources, indicating that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks. Strong interlaminar inhibitory inputs are found, particularly for excitatory neurons in layers 2/3 and 5. This differs from earlier studies reporting that inhibitory cortical connections to excitatory neurons are generally localized within the same cortical layer. On the basis of the functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory cells at single cell resolution, establishing precise layer‐by‐layer synaptic wiring diagrams of excitatory neurons in the visual cortex.

Abbreviations

aCSF

artificial cerebrospinal fluid

DAPI

4′‐6‐diamidino‐2‐phenylindole

LSPS

laser scanning photostimulation

V1

primary visual cortex

     

Local lateral connectivity of inhibitory clutch cells in layer 4 of cat visual cortex (area 17)

To characterise spatially a major component of the anatomical basis of local lateral inhibition in layer 4 of cat visual cortex (area 17), we analysed the lateral distribution of neuronal somata postsynaptic to electrophysiologically characterised GABAergic clutch (basket) cell axons (CC1 and CC2). We report two main results. First, the clutch cell axons appear to show isotropic lateral connectivity near their cell body (less than 50 μm radius), but beyond this core region they show anisotropic lateral connectivity, preferring particular angular sectors around their cell body. Second, we estimated the probability of lateral connection for each axon arbor as a function of radial distance from the parent soma. We found that this radial function has a brief rising phase, to a peak at 30–45 μm, and a longer, exponential decaying phase, with a space constant of around 50 μm. The shape of the radial connection probability function suggests that most lateral inhibitory connections of clutch cells are formed with neurons in nearest-neighbour cortical columns. Taken together, the results suggest that these individual layer-4 clutch cell axons may inhibit all (isotropic) nearest-neighbour cortical columns with a relatively high probability of connection, but outside this core region may provide a type of anisotropic lateral inhibition of cortical columns with a radially decreasing probability of connection. Electronic Publication     

Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex

A basic feature of the neocortex is its organization in functional, vertically oriented columns, recurring modules of signal processing and a system of transcolumnar long-range horizontal connections. These columns, together with their network of neurons, present in all sensory cortices, are the cellular substrate for sensory perception in the brain. Cortical columns contain thousands of neurons and span all cortical layers. They receive input from other cortical areas and subcortical brain regions and in turn their neurons provide output to various areas of the brain. The modular concept presumes that the neuronal network in a cortical column performs basic signal transformations, which are then integrated with the activity in other networks and more extended brain areas. To understand how sensory signals from the periphery are transformed into electrical activity in the neocortex it is essential to elucidate the spatial-temporal dynamics of cortical signal processing and the underlying neuronal ‘microcircuits’. In the last decade the ‘barrel’ field in the rodent somatosensory cortex, which processes sensory information arriving from the mysticial vibrissae, has become a quite attractive model system because here the columnar structure is clearly visible. In the neocortex and in particular the barrel cortex, numerous neuronal connections within or between cortical layers have been studied both at the functional and structural level. Besides similarities, clear differences with respect to both physiology and morphology of synaptic transmission and connectivity were found. It is therefore necessary to investigate each neuronal connection individually, in order to develop a realistic model of neuronal connectivity and organization of a cortical column. This review attempts to summarize recent advances in the study of individual microcircuits and their functional relevance within the framework of a cortical column, with emphasis on excitatory signal flow.     

Functional interactions among neurons in inferior temporal cortex of the awake macaque

Summary Functional interactions among inferior temporal cortex (IT) neurons were studied in the awake, fixating macaque monkey during the presentation of visual stimuli. Extracellular recordings were obtained simultaneously from several microelectrodes, and in many cases, spike trains from more than one neuron were extracted from each electrode by the use of spike shape sorting technology. Functional interactions between pairs of neurons were measured using cross-correlation. Discharge patterns of single neurons were evaluated using auto-correlation and PST histograms. Neurons recorded on the same electrode (within about 100 n) had more similar stimulus selectivity and were more likely to show functional interactions than those recorded on different electrodes spaced about 250 to 500 microns apart. Most neurons tended to fire in bursts tens to hundreds of milliseconds in duration, and asynchronously from the stimulus induced rate changes. Correlated neuronal firing indicative of shared inputs and direct interactions was observed. Occurrence of shared input was significantly lower for neuron pairs recorded on different electrodes than for neurons recorded on the same electrode. Direct connections occurred about as often for neurons on different electrodes as for neurons on the same electrode. These results suggest that input projections are usually restricted to less than 500 m patches and are then distributed over greater distances by intrinsic connections. Measurements of synaptic contribution suggest that typically more than 5 near-simultaneous inputs are required to cause an IT neuron to discharge.