Intracortical Network Effects Preserve Thalamocortical Input Efficacy in a Cortex Without Layers

Abstract

Layer IV (LIV) of the rodent somatosensory cortex contains the somatotopic barrel field. Barrels receive much of the sensory input to the cortex through innervation by thalamocortical axons from the ventral posteromedial nucleus. In the reeler mouse, the absence of cortical layers results in the formation of mispositioned barrel-equivalent clusters of LIV fated neurons. Although functional imaging suggests that sensory input activates the cortex, little is known about the cellular and synaptic properties of identified excitatory neurons of the reeler cortex. We examined the properties of thalamic input to spiny stellate (SpS) neurons in the reeler cortex with in vitro electrophysiology, optogenetics, and subcellular channelrhodopsin-2-assisted circuit mapping (sCRACM). Our results indicate that reeler SpS neurons receive direct but weakened input from the thalamus, with a dispersed spatial distribution along the somatodendritic arbor. These results further document subtle alterations in functional connectivity concomitant of absent layering in the reeler mutant. We suggest that intracortical amplification mechanisms compensate for this weakening in order to allow reliable sensory transmission to the mutant neocortex.

The Functioning of a Cortex without Layers

“…Molecular markers typically expressed in a layer-specific fashion are still expressed by displaced neurons (Katsuyama and Terashima, 2009; Boyle et al, 2011; Wagener et al, 2016), suggesting that their molecular identity is not compromised by the lack of lamination. The morphology of defined neuronal types has been investigated in some detail and is relatively unchanged (Guy et al, 2016), although some excitatory types see a reduction in the number of dendritic spines (Niu et al, 2008), and some inhibitory types have longer dendrites with more branches (Yabut et al, 2007). …”

“…Of course one may wonder whether these morphologically aberrant reeler neurons have also aberrant electrophysiological properties. However, what little evidence exists shows that differences are slim: neurons in the neocortex and the hippocampus retain normal firing patterns and most other intrinsic properties (Silva et al, 1991; Kowalski et al, 2010; Guy et al, 2016). …”

“…(A) Regular-spiking spiny stellate cell ( red arrow ), located on top of two barrel equivalents ( asterisks ; labeled by Sccn1a-cre/tdTomato; see Guy et al, 2015, 2016). Please note that the dendrites spread out in a V-shaped manner to reach to neighboring cell clusters whereas the axon ( red arrowhead ) initially is directed toward the pial surface ( dashed line ).…”

“…Still in the hippocampus in vitro , Kowalski et al (2010) showed that mossy cells of the hilar region of the dentate gyrus receive direct input from granule cells in both mutant and normal mice. Using channelrhodopsin expression to control thalamocortical fiber activity and whole cell recordings in vitro , our group provided evidence that spiny stellate neurons, a main constituent of barrels in the somatosensory cortex, receive strong direct input from the ventral posteromedial nucleus in reeler, as they do in normal animals (Guy et al, 2016; Wagener et al, 2016). A few studies investigated the receptive field properties of individual neurons in the reeler visual cortex with single unit, extracellular recordings.…”

“…In line with this role in synaptic transmission, reelin was also shown to enhance hippocampal long-term potentiation (Beffert et al, 2005; Qiu et al, 2006b). In addition, evidence is mounting that GABAergic transmission is weakened by a loss of reelin, resulting in a shift in the excitation-inhibition balance with potentially far-reaching consequences (Qiu et al, 2006a; Guy et al, 2016; Bouamrane et al, 2017). Finally, at least one study reported a slight anomaly in visual perception in reeler mice, namely impairment in orientation discrimination (Pielecka-Fortuna et al, 2015).…”