This review of neocortical layer 6 focuses on primary sensory regions, largely because layer 6 has been more thoroughly studied in these regions than in motor, or association areas. This is not to say that layer 6 has been comprehensively investigated in any region, or that it is possible to define all aspects of its structure and function, in any region. In fact, for many reasons, layer 6 has been studied in rather less detail than layers 3, 4 and 5 and it has been necessary here to correlate information from a range of different types of study, different cortical regions and different species, in an attempt to place the knowledge we have in something approaching a functional context. These correlations have been hampered by the fundamental limitations of each technique. For example, in many in vivo extracellular recording studies, the type of neurones recorded could not be identified. This limits the conclusions that can be drawn about the response properties of the several sub-types of layer 6 neurones and any structure-function relationships that might pertain. A number of elegant anatomical studies form the essential platform upon which much of the discussion here resides, but all too few functional studies have even attempted to place their findings in this context.
Layer 6 remains something of an enigma. Some of the cells in this layer receive direct thalamo-cortical input, placing layer 6 with layer 4 as a sensory input layer. It is also, however, an important output layer, from which large descending projections to many thalamic nuclei arise. Moreover, the several subclasses of corticothalamic neurones constitute only some 30–50% of the pyramidal cells in layer 6. Layer 6 corticocortical (CC) cells form another large group of pyramidal cells that send long horizontal axons which form connections across cortical columns and cortical areas, eg. somatosensory and motor. The fourth major class of pyramidal cells projects to the claustrum in addition to sending long horizontal axons through the deep cortical layers. At the end of each section is a summary in italics.
A note on nomenclature
In the literature, discussion of different regions of thalamus uses the terms primary sensory, or ‘specific’ to describe the thalamic nuclei or regions that receive direct excitatory input from the periphery, eg. from the retina, or from the trigeminal nucleus. Regions that receive sensory input indirectly, via the cortex, have often been rather loosely termed ‘non-specific’ or association regions. In this review, the term ‘primary sensory’ is used to describe those thalamic regions that receive sensory input directly from the periphery. Similarly, to assist those less familiar with the cytoarchitectonically identifiable regions of sensory and association cortex, the term primary sensory cortex is used broadly here to describe those regions that receive thalamo-cortical input from primary sensory regions of thalamus, eg. V1 (primary visual cortex, Brodmann's area 17), SmI (or SI, somatosensory, areas 1–3), or AI (auditory, areas 41, 42). Secondary sensory refers to those cortical regions that receive sensory information directly from primary regions and association regions of cortex, rather loosely to define cortical regions that receive sensory information via cortex and ‘non-specific’, or association thalamus.