A Neural Circuit That Controls Cortical State, Plasticity, and the Gain of Sensory Responses in Mouse

Abstract

Neurons in the visual cortex were first found to be exquisitely selective for particular properties of visual stimuli in anesthetized animals, including mice. Studies of alert mice in an apparatus that allowed them to stand or run revealed that locomotion causes a change in cortical state that dramatically increases the magnitude of responses in neurons of the visual cortex without altering selectivity, effectively changing the gain of sensory responses. Locomotion also dramatically enhances adult plasticity in the recovery from long-term visual deprivation. We have studied the elements and operation of the neural circuit responsible for the enhancement of activity and shown that it enhances plasticity even in mice not free to run. The circuit consists of projections ascending from the midbrain locomotor region (MLR) to the basal forebrain, activating cholinergic and perhaps other projections to excite inhibitory interneurons expressing vasoactive intestinal peptide (VIP) in the visual cortex. VIP cells activated by locomotion inhibit interneurons that express somatostatin (SST), thereby disinhibiting the excitatory principal neurons and allowing them to respond more strongly to effective visual stimuli. These findings reveal in alert animals how the ascending reticular activating system described in anesthetized animals 50 years ago operates to control cortical state.

Role of somatostatin-positive cortical interneurons in the generation of sleep slow waves

“…Another question is how the activity and excitability of SOM+ cells is controlled by subcortical wake and sleep promoting systems, either directly or through other cortical cell types. SOM+ cells are inhibited by cortical VIP interneurons [44] that fire during locomotion and are themselves under the control of arousal systems [45] and by PV+ interneurons in the basal forebrain, which are wake-on and promote wake [43]. Also, noradrenaline, a neuromodulator that is released at high levels in wake and low levels in sleep, reduces the effectiveness of synapses between SOM+ and pyramidal cells [46] and the conductivity of gap junctions [47], possibly preventing the induction and synchronization of sleep slow waves.…”

Reducing GABAA-mediated inhibition improves forelimb motor function after focal cortical stroke in mice

“…Indeed, our neuroanatomical analyses revealed a significant reduction of two major populations of GABAergic cortical interneurons after the infarct. Somatostatin-containing interneurons represent a low-threshold inhibitory population involved in cortical plasticity666768 whereas parvalbumin-positive fast-spiking interneurons play important roles in control of network firing due to their perisomatic synapses onto pyramidal cells48. It remains to be established whether loss of SOM and PV immunoreactivity is due to cell loss or down-regulation of the expression of these markers.…”

Treatment of amblyopia as a function of age

“…Evidence suggests that motor-related signals can gain access to the visual cortex via two different 'neuromodulatory' routes. One is carried by acetylcholinergic afferents from the basal forebrain to the parvalbumin cells, resulting in disinhibition of visual cortical circuits in the visual cortex (Stryker, 2014). The other involves a more direct excitatory input from the nuclei of the visual thalamus (including the lateral geniculate nucleus) that is probably inherited from the head and body movement-related activity in the superior colliculus (Roth et al, 2016).…”