An Ultrastructural Study of the Thalamic Input to Layer 4 of Primary Motor and Primary Somatosensory Cortex in the Mouse

Abstract

The traditional classification of primary motor cortex (M1) as an agranular area has been challenged recently when a functional layer 4 (L4) was reported in M1. L4 is the principal target for thalamic input in sensory areas, which raises the question of how thalamocortical synapses formed in M1 in the mouse compare with those in neighboring sensory cortex (S1). We identified thalamic boutons by their immunoreactivity for the vesicular glutamate transporter 2 (VGluT2) and performed unbiased disector counts from electron micrographs. We discovered that the thalamus contributed proportionately only half as many synapses to the local circuitry of L4 in M1 compared with S1. Furthermore, thalamic boutons in M1 targeted spiny dendrites exclusively, whereas ϳ9% of synapses were formed with dendrites of smooth neurons in S1. VGluT2 ϩ boutons in M1 were smaller and formed fewer synapses per bouton on average (1.3 vs 2.1) than those in S1, but VGluT2 ϩ synapses in M1 were larger than in S1 (median postsynaptic density areas of 0.064 m 2 vs 0.042 m 2 ). In M1 and S1, thalamic synapses formed only a small fraction (12.1% and 17.2%, respectively) of all of the asymmetric synapses in L4. The functional role of the thalamic input to L4 in M1 has largely been neglected, but our data suggest that, as in S1, the thalamic input is amplified by the recurrent excitatory connections of the L4 circuits. The lack of direct thalamic input to inhibitory neurons in M1 may indicate temporal differences in the inhibitory gating in L4 of M1 versus S1.

Multiscale dynamics and information flow in a data-driven model of the primary motor cortex microcircuit

“…Cell properties, locations, and local and long-range connectivity were largely derived from a coherent set of experimental data obtained using the same techniques in a single lab and single species, with a focus on two deep (L5) populations of particular interest: corticospinal cells and corticostriatal cells. One innovative feature in the network presented here was the inclusion of a Layer 4 for motor cortex, consistent with its recent characterization 141,14,10 . The model was developed using NEURON and NetPyNE 23,37 .…”

“…Mouse cortical depth and boundaries for layers 2/3, 4, 5A, 5B and 6 were based on our published experimental data 139,3,141 . Although traditionally M1 has been considered an agranular area lacking layer 4, we recently identified M1 pyramidal neurons with the expected prototypical physiological, morphological and wiring properties of layer 4 neurons 141 (see also 14,10 ), and therefore incorporated this layer in the model.…”

Assembly of Excitatory Synapses in the Absence of Glutamatergic Neurotransmission

“…Indeed, staining for VGlut2, which is enriched in terminals of thalamic axons (Bopp et al, 2017), and recordings of EPSCs from layer IV of the somatosensory cortex suggested that thalamic inputs onto Syb2-deficient cortical neurons formed (Figure S3J and Table S1). We therefore primarily focused on the hippocampus, which is comprised of and largely innervated by glutamatergic neurons of the Emx1 lineage (Gorski et al, 2002).…”

Systematic Integration of Structural and Functional Data into Multi-Scale Models of Mouse Primary Visual Cortex

“…The second step, only applicable to the biophysical model, determines the number and placement of synapses on V1 neurons, using data on LGN axonal density in V1 (Morgenstern, Bourg and Petreanu, 2016) and estimates of synapse numbers per neuron (Schoonover et al, 2014;Bopp et al, 2017). The effect of dendritic placement on the somatic charge conductance is shown in Fig.…”

“…Various studies have identified the thalamic innervation pattern into the visual cortex across laminae Scanziani, 2013, 2018;Kloc and Maffei, 2014;Schoonover et al, 2014;Ji et al, 2015;Morgenstern, Bourg and Petreanu, 2016;Bopp et al, 2017). We used these results to identify the total current that different cell classes should receive from the LGN.…”