SALIENT FEATURES OF SYNAPTIC ORGANIZATION IN THE CEREBRAL-CORTEX

The neuronal and synaptic organisation of the cerebral cortex appears exceedingly complex, and the definition of a basic cortical circuit in terms of defined classes of cells and connections is necessary to fac ilitate progress of its analysis. During the last two decades quantita tive studies of the synaptic connectivity of identified cortical neuro nes and their molecular dissection revealed a number of general rules that apply to all areas of cortex. In this review, first the precise l ocation of postsynaptic GABA and glutamate receptors is examined at co rtical synapses, in order to define the site of synaptic interactions. It is argued that, due to the exclusion of G protein-coupled receptor s from the postsynaptic density, the presence of extrasynaptic recepto rs and the molecular compartmentalisation of the postsynaptic membrane , the synapse should include membrane areas beyond the membrane specia lisation. Subsequently, the following organisational principles are ex amined: 1. The cerebral cortex consists of: (i) a large population of principal neurones reciprocally connected to the thalamus and to each other via axon collaterals releasing excitatory amino acids, and, (ii) a smaller population of mainly local circuit GABAergic neurones. 2. D ifferential reciprocal connections are also formed amongst GABAergic n eurones. 3. Al extrinsic and intracortical glutamatergic pathways term inate on both the principal and the GABAergic neurones, differentially weighted according to the pathway. 4. Synapses of multiple sets of gl utamatergic and GABAergic afferents subdivide the surface of cortical neurones and are often co-aligned on the dendritic domain. 5. A unique feature of the cortex is the GABAergic axo-axonic cell, influencing p rincipal cells through GABAA receptors at synapses located exclusively on the axon initial segment. The analysis of these salient features o f connectivity has revealed a remarkably selective array of connection s, yet a highly adaptable design of the basic circuit emerges when com parisons are made between cortical areas or layers. The basic circuit is most obvious in the hippocampus where a relatively homogeneous set of spatially aligned principal cells allows an easy visualization of t he organisational rules. Those principles which have been examined in the isocortex proved to be identical or very similar. In the isocortex , the basic circuit, scaled to specific requirements, is repeated in e ach layer. As multiple sets of output neurones evolved, requiring subt ly different needs for their inputs, the basic circuit may be superimp osed several times in the same layer. Tangential intralaminar connecti ons in both the hippocampus and isocortex also connect output neurones with similar properties, as best seen in the patchy connections in th e isocortex. The additional radial superposition of several laminae of distinct sets of output neurones, each representing and supported by its basic circuit, requires a co-ordination of their activity that is mediated by highly selective interlaminar connections, involving both the GABAergic and the excitatory amino acid releasing neurones. The re markable specificity in the geometry of cells and the selectivity in p lacement of neurotransmitter receptors and synapses on their surface, strongly suggest a predominant role for time in the coding of informat ion, but this does not exclude an important role also for the rate of action potential discharge in cortical representation of information. (C) 1998 Elsevier Science B.V. All rights reserved.