Morphological heterogeneity of layer VI neurons in mouse barrel cortex

Abstract

Understanding the basic neuronal building blocks of the neocortex is a necessary first step toward comprehending the composition of cortical circuits. Neocortical layer VI is the most morphologically diverse layer and plays a pivotal role in gating information to the cortex via its feedback connection to the thalamus and other ipsilateral and callosal corticocortical connections. The heterogeneity of function within this layer is presumably linked to its varied morphological composition. However, so far, very few studies have attempted to define cell classes in this layer using unbiased quantitative methodologies. Utilizing the Golgi staining technique along with the Neurolucida software, we recontructed 222 cortical neurons from layer VI of mouse barrel cortex. Morphological analyses were performed by quantifying somatic and dendritic parameters, and, by using principal component and cluster analyses, we quantitatively categorized neurons into six distinct morphological groups. Additional systematic replication on a separate population of neurons yielded similar results, demonstrating the consistency and reliability of our categorization methodology. Subsequent post hoc analyses of dendritic parameters supported our neuronal classification scheme. Characterizing neuronal elements with unbiased quantitative techniques provides a framework for better understanding structure-function relationships within neocortical circuits in general. Indexing terms neocortex layer VI; Golgi; neuronal morphology; barrel cortexThe neocortex is composed of six distinct layers, with each layer containing different morphological phenotypes that presumably subserve different processing roles (Mountcastle, 1997). For example, the excitatory spiny stellate cells and small pyramidal neurons in layer IV receive strong thalamo-cortical input (see Davis and Sterling, 1979;White, 1989). By contrast, the excitatory neurons of the infragranular layers (V and VI) are composed predominantly of larger pyramidal cells (Jones, 1984;White, 1989;Rocco and Brumberg, 2007). Although layer IV is the principal input layer, layers V and VI originate most of the cortical output (Jones, 1984;White, 1989). Within the infragranular layers, layer VI is of particular interest, primarily because of the diverse population of neurons and its complicated microcircuitry. Layer VI receives thalamic and cortical inputs and gives rise to corticothalamic feedback projections as well as corticocortical, corticoclaustral, and commissural fibers (Tombol, 1984;Katz, 1987;

Synaptic Microcircuits in the Barrel Cortex

“…Excitatory L6 neurons are markedly more heterogenous than those of other cortical layers, both with respect to their dendritic and axonal morphology. In particular excitatory L6B neurons in the barrel cortex have many distinct morphologies ranging from short, untufted pyramids with apical dendrites that terminate in layer 5, those with atypically oriented (oblique, horizontal or inverted) 'apical' dendrites to multipolar neurons without a main dendrite [127,139]. This is in accordance with L6B neuronal morphologies described for other cortical areas [140][141][142].…”

“…4.5d). In addition, a small population of L6A pyramidal cells with apical dendrites ascending to layer 1 or those with obliquely oriented main dendrites were also found [49,56,57,127]. L6A pyramidal cells can be subdivided into at least two major groups: those with a predominantly intracortical axonal projection pattern and those with an axon that projects back to the thalamic nuclei [55-57, 128, 129; see also [130] for a review).…”

Heterogeneity in dendritic morphology of moth antennal lobe projection neurons

“…Cortical interneurons often show physiological and morphological diversity (Ascoli et al, 2008;Lledo et al, 2008), and diversity of the principal cells in the cortex has been reported for the mouse cerebral cortex (Chen et al, 2009) and olfactory bulb (Padmanabhan and Urban, 2010). Neuronal diversity seems to be universal in the nervous system and is probably important for normal functioning (Marder and Goaillard, 2006).…”

Orexin-dependent activation of layer VIb enhances cortical network activity and integration of non-specific thalamocortical inputs

“…The innermost layer VI is further partitioned into an upper part (layer VIa) containing a high density of glutamatergic pyramidal neurons and a deeper part (layer VIb) dominated by polymorphic non-pyramidal neurons (Töm-böl 1984;van Brederode and Snyder 1992;Zhang and Deschenes 1997;Mercer et al 2005;Andjelic et al 2009;Chen et al 2009;Marx and Feldmeyer 2013).…”