Gamma band rhythms may synchronize distributed cell assemblies to facilitate information transfer within and across brain areas, yet their underlying mechanisms remain hotly debated. Most circuit models pose that soma-targeting parvalbumin (PV) positive GABAergic neurons are the essential inhibitory neuron subtype necessary for gamma rhythms. Using cell-type specific optogenetic manipulations in behaving animals, we show that dendrite-targeting somatostatin (SOM) interneurons are critical for a visually induced, context-dependent gamma rhythm in the visual cortex (V1). A novel computational model independently predicts that context-dependent gamma rhythms depend critically on SOM interneurons. Further in vivo experiments show that SOM neurons are required for long distance coherence across V1. Taken together, these data establish a new mechanism for synchronizing distributed networks in the visual cortex. By operating through dendritic and not just somatic inhibition, SOM-mediated oscillations may expand the computational power of gamma rhythms for optimizing the synthesis and storage of visual perceptions.

SummaryAnatomical and physiological experiments have outlined a blueprint for the feed-forward flow of activity in cortical circuits: signals are thought to propagate primarily from the middle cortical layer, L4, up to L2/3, and down to the major cortical output layer, L5. Pharmacological manipulations, however, have contested this model and suggested that L4 may not be critical for sensory responses of neurons in either superficial or deep layers. To address these conflicting models we reversibly manipulated L4 activity in awake, behaving mice using cell-type specific optogenetics. In contrast to both prevailing models, we show that activity in L4 directly suppresses L5, in part by activating deep, fast spiking inhibitory neurons. Our data suggest that the net impact of L4 activity is to sharpen the spatial representations of L5 neurons. Thus we establish a novel translaminar inhibitory circuit in the sensory cortex that acts to enhance the feature selectivity of cortical output.

SUMMARY The neural substrates and pathophysiological mechanisms underlying the onset of cognitive and motor deficits in autism spectrum disorders (ASDs) remain unclear. Mutations in ASD-associated SHANK3 in mice (Shank3B−/−) result in the accelerated maturation of corticostriatal circuits during the second and third postnatal weeks. Here, we show that during this period, there is extensive remodeling of the striatal synaptic proteome and a developmental switch in glutamatergic synaptic plasticity induced by cortical hyperactivity in striatal spiny projection neurons (SPNs). Behavioral abnormalities in Shank3B−/− mice emerge during this stage and are ameliorated by normalizing excitatory synapse connectivity in medial striatal regions by the downregulation of PKA activity. These results suggest that the abnormal postnatal development of striatal circuits is implicated in the onset of behavioral deficits in Shank3B−/− mice and that modulation of postsynaptic PKA activity can be used to regulate corticostriatal drive in developing SPNs of mouse models of ASDs and other neurodevelopmental disorders.

Cortical gamma oscillations have been implicated in a variety of cognitive, behavioral, and circuit-level phenomena. However, the circuit mechanisms of gamma-band generation and synchronization across cortical space remain uncertain. Using optogenetic patterned illumination in acute brain slices of mouse visual cortex, we define a circuit composed of layer 2/3 (L2/3) pyramidal cells and somatostatin (SOM) interneurons that phase-locks ensembles across the retinotopic map. The network oscillations generated here emerge from non-periodic stimuli, and are stimulus size-dependent, coherent across cortical space, narrow band (30 Hz), and depend on SOM neuron but not parvalbumin (PV) neuron activity; similar to visually induced gamma oscillations observed in vivo. Gamma oscillations generated in separate cortical locations exhibited high coherence as far apart as 850 μm, and lateral gamma entrainment depended on SOM neuron activity. These data identify a circuit that is sufficient to mediate long-range gamma-band coherence in the primary visual cortex.