In vivo Dissection of Long Range Inputs to the Rat Barrel Cortex

Layer 1 (L1) of the cerebral cortex is a largely acellular layer that consists mainly of long-range projection axons and apical dendrites of deeper pyramidal neurons. In the rodent barrel cortex, L1 contains axons from both higher motor and sensory areas of the brain. Despite the abundance of synapses in L1 their actual contribution to sensory processing remains unknown. We investigated the impact of activating long-range axons on barrel cortex L2/3 pyramidal neurons in vivo using a combination of optogenetics and eletrophysiological techniques. The reason we target our investigation on L2/3 is because of its well-known sparse sensory responses. We hypothesize that long-range top-down inputs via L1 can provide the additional inputs necessary to unleash L2/3 and strongly influence sensory processing in S1. We focused on three main sources of BC-projecting synapses: the posterior medial nucleus of the thalamus (POm, the secondary somatosensory nucleus), the primary motor cortex (M1), and the secondary somatosensory cortex (S2). Here we report that while activation of POm axons elicits strong EPSPs in most recorded L2/3 cells, activation of M1 or S2 axons elicited small or no detectable responses. Only POm activation boosted sensory responses in L2/3 pyramidal neurons. We also found that during wakefulness and under sedation, POM activation not only elicited a strong fast-onset EPSP in L2/3 neurons, but also a delayed persistent response. Pharmacological inactivation of POM abolished this persistent response but not the initial synaptic volley to L2/3. We conclude that the persistent response requires intrathalamic or thalamocortical circuits and cannot be mediated by specialized synaptic terminals or intracortical circuitry. Overall, our study suggests that the higher order thalamic nucleus provides more powerful network effect on L2/3 sensory processing than higher order cortical feedback inputs. POm activation not only directly boosts L2/3 sensory responses, but is also capable of influencing S1 signal processing for prolonged periods of time after stimulus onset and can potentially be important for other cognitive aspects of sensory computation.