To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of specific neuronal populations. Despite the successful application of retrograde transsynaptic viruses for identifying presynaptic neurons of transduced neurons, analogous anterograde transsynaptic tools for tagging postsynaptically targeted neurons remain under development. Here, we report that adeno-associated virus (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties. AAV1-Cre from transduced presynaptic neurons effectively and specifically drove Cre-dependent transgene expression in selected postsynaptic neuronal targets, and thus allowed the tracing and functional manipulation of axonal projections from the latter input-defined neuronal population. Application of this tool in superior colliculus (SC) revealed that SC neuron subpopulations receiving corticocollicular projections from auditory and visual cortex specifically drove flight and freezing, two different types of defense behavior, respectively. Such anterograde transsynaptic tagging is thus useful for forward screening of distinct functional neural pathways embedded in complex brain circuits.

Cortical sensory processing is modulated by behavioral and cognitive states. How the modulation is achieved through impacting synaptic circuits remains largely unknown. In awake mouse auditory cortex, we reported that sensory-evoked spike responses of layer 2/3 (L2/3) excitatory cells were scaled down with preserved sensory tuning when animals transitioned from quiescence to active behaviors, while L4 and thalamic responses were unchanged. Whole-cell voltage-clamp recordings further revealed that tone-evoked synaptic excitation and inhibition exhibited a robust functional balance. Changes of behavioral state caused scaling down of excitation and inhibition at an approximately equal level in L2/3 cells, but no synaptic changes in L4 cells. This laminar-specific gain control could be attributed to an enhancement of L1–mediated inhibitory tone, with L2/3 parvalbumin inhibitory neurons suppressed as well. Thus, L2/3 circuits can adjust the salience of output in accordance with momentary behavioral demands while maintaining the sensitivity and quality of sensory processing.

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