Cell type specific connections from primary motor to primary somatosensory cortex.

Anatomical studies have shown that primary somatosensory (S1) and primary motor (M1) cortices are reciprocally connected. The pathway from primary motor cortex (M1) to primary somatosensory cortex (S1) is thought to influence activity in S1 by conveying a general modulatory signal and/or a copy of the motor command. In these studies, we investigated M1 synaptic inputs to S1 by injecting an AAV virus containing channelrhodopsin-2 and a fluorescent tag into M1. Consistent with previous results, we found labeling of M1 axons within S1 that was most robust in the deep layers and in L1. We recorded in vitro from excitatory neurons and two classes of inhibitory interneurons, fast-spiking and somatostatin-expressing inhibitory interneurons. All three cell types had a high probability of receiving direct excitatory M1 input, with both excitatory and inhibitory cells in L4 being the least likely to receive input from M1. Disynaptic inhibition was observed frequently, indicating that M1 recruits substantial inhibition within S1. A subpopulation of pyramidal neurons in layers 5 and 6 received especially strong input from M1, suggesting M1 differentially contacts classes of pyramidal neurons, such as those projecting to different sensorimotor centers at cortical and subcortical levels. We tested this hypothesis by combining optogenetic techniques to specifically label M1 synaptic inputs to S1 and retrograde tracing to identify specific populations of projection neurons in infragranular layers of S1. We determined that both the intrinsic properties and the magnitude of M1 input to an S1 pyramidal neuron is highly dependent on its projection target. Overall, our results suggest that activation of M1 evokes within S1 a general increase in excitatory and inhibitory synaptic activity that could contribute in a layer-specific manner to state-dependent changes in S1. Our results further indicate that M1 may specifically engage subcircuits within S1 in order to differentially regulate particular downstream cortical and subcortical processing centers

Postnatal maturation of somatostatin-expressing inhibitory cells in the somatosensory cortex of GIN mice

Postnatal inhibitory neuron development affects mammalian brain function, and failure of this maturation process may underlie pathological conditions such as epilepsy, schizophrenia, and depression. Furthermore, understanding how physiological properties of inhibitory neurons change throughout development is critical to understanding the role(s) these cells play in cortical processing. One subset of inhibitory neurons that may be affected during postnatal development is somatostatin-expressing (SOM) cells. A subset of these cells is labeled with green-fluorescent protein (GFP) in a line of mice known as the GFP-positive inhibitory neurons (GIN) line. Here, we studied how intrinsic electrophysiological properties of these cells changed in the somatosensory cortex of GIN mice between postnatal ages P11 and P32+. GIN cells were targeted for whole-cell current-clamp recordings and ranges of positive and negative current steps were presented to each cell. The results showed that as the neocortical circuitry matured during this critical time period multiple intrinsic and firing properties of GIN inhibitory neurons, as well as those of excitatory (regular-spiking [RS]) cells, were altered. Furthermore, these changes were such that the output of GIN cells, but not RS cells, increased over this developmental period. We quantified changes in excitability by examining the input–output relationship of both GIN and RS cells. We found that the firing frequency of GIN cells increased with age, while the rheobase current remained constant across development. This created a multiplicative increase in the input–output relationship of the GIN cells, leading to increases in gain with age. The input–output relationship of the RS cells, on the other hand, showed primarily a subtractive shift with age, but no substantial change in gain. These results suggest that as the neocortex matures, inhibition coming from GIN cells may become more influential in the circuit and play a greater role in the modulation of neocortical activity