Single dendrite-targeting interneurons generate branch-specific inhibition.

Microcircuits composed of dendrite-targeting inhibitory interneurons and pyramidal cells (PCs) are fundamental elements of cortical networks, however, the impact of individual interneurons on pyramidal dendrites is unclear. Here, we combine paired recordings and calcium imaging to determine the spatial domain over which single dendrite-targeting interneurons influence PCs in olfactory cortex. We show that a major action of individual interneurons is to inhibit dendrites in a branch-specific fashion.

From dendrite to soma: dynamic routing of inhibition by complementary interneuron microcircuits in olfactory cortex.

Diverse inhibitory pathways shape cortical information processing; however, the relevant interneurons recruited by sensory stimuli and how they impact principal cells are unclear. Here we show that two major interneuron circuits govern dynamic inhibition in space and time within the olfactory cortex. Dendritic-targeting layer 1 interneurons receive strong input from the olfactory bulb and govern early-onset feedforward inhibition. However, this circuit is only transiently engaged during bursts of olfactory bulb input. In contrast, somatic-targeting layer 3 interneurons, recruited exclusively by recurrent excitation from pyramidal cells, produce late-onset feedback inhibition. Our results reveal two complementary interneuron circuits enforcing widespread inhibition, which shifts from the apical dendrites to somata of pyramidal cells during bursts of sensory input.

Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis.

The establishment of neural circuitry requires vast numbers of synapses to be generated during a specific window of brain development, but it is not known why the developing mammalian brain has a much greater capacity to generate new synapses than the adult brain. Here we report that immature but not mature astrocytes express thrombospondins (TSPs)-1 and -2 and that these TSPs promote CNS synaptogenesis in vitro and in vivo. TSPs induce ultrastructurally normal synapses that are presynaptically active but postsynaptically silent and work in concert with other, as yet unidentified, astrocyte-derived signals to produce functional synapses. These studies identify TSPs as CNS synaptogenic proteins, provide evidence that astrocytes are important contributors to synaptogenesis within the developing CNS, and suggest that TSP-1 and -2 act as a permissive switch that times CNS synaptogenesis by enabling neuronal molecules to assemble into synapses within a specific window of CNS development.