Highlights d S1 provides stronger input to striatal PV neurons than spiny projection neurons d M1 provides equal input to striatal PV neurons and spiny projections neurons d S1-and M1-corticostriatal inputs exert opposing influence on choice behavior d Manipulation of striatal PV neurons bidirectionally influences choice behavior

In the developing visual system before eye opening, spontaneous retinal waves trigger bursts of neural activity in downstream structures, including visual cortex. At the same ages when retinal waves provide the predominant input to the visual system, sleep is the predominant behavioral state. However, the interactions between behavioral state and retinal wave-driven activity have never been explicitly examined. Here we characterized unit activity in visual cortex during spontaneous sleep-wake cycles in 9- and 12-day-old rats. At both ages, cortical activity occurred in discrete rhythmic bursts, ~30-60 s apart, mirroring the timing of retinal waves. Interestingly, when pups spontaneously woke up and moved their limbs in the midst of a cortical burst, the activity was suppressed. Finally, experimentally evoked arousals also suppressed intraburst cortical activity. All together, these results indicate that active wake interferes with the activation of the developing visual cortex by retinal waves. They also suggest that sleep-wake processes can modulate visual cortical plasticity at earlier ages than has been previously considered. By recording in visual cortex in unanesthetized infant rats, we show that neural activity attributable to retinal waves is specifically suppressed when pups spontaneously awaken or are experimentally aroused. These findings suggest that the relatively abundant sleep of early development plays a permissive functional role for the visual system. It follows, then, that biological or environmental factors that disrupt sleep may interfere with the development of these neural networks.

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The striatum is the main input nucleus of the basal ganglia and is a key site of sensorimotor integration. While the striatum receives extensive excitatory afferents from the cerebral cortex, the influence of different cortical areas on striatal circuitry and behavior is unknown. Here we find that corticostriatal inputs from whisker-related primary somatosensory (S1) and motor (M1) cortex differentially innervate projection neurons and interneurons in the dorsal striatum, and exert opposing effects on sensory-guided behavior. Optogenetic stimulation of S1-corticostriatal afferents in ex vivo recordings produced larger postsynaptic potentials in striatal parvalbumin (PV)-expressing interneurons than D1-or D2-expressing spiny projection neurons (SPNs), an effect not observed for M1-corticostriatal afferents. Critically, in vivo optogenetic stimulation of S1-corticostriatal afferents produced task-specific behavioral inhibition, which was bidirectionally modulated by striatal PV interneurons. Optogenetic stimulation of M1 afferents produced the opposite behavioral effect. Thus, our results suggest opposing roles for sensory and motor cortex in behavioral choice via distinct influences on striatal circuitry. Results Optogenetic activation of S1 or M1 corticostriatal afferents differentially engage striatal neuronsWe used optogenetic activation of corticostriatal afferents from S1 or M1 with channelrhodopsin-2 (ChR2) combined with ex vivo whole cell current clamp recordings of identified striatal neurons to determine the striatal circuitry engaged by corticostriatal input from different sources ( Figure 1A ). We chose to investigate the anterior dorsal striatum because of prominent overlap between S1 and M1 inputs in this region ( Supplemental Figure 1 ) [3,4] . Striatal D1-SPNs, D2-SPNs and PV interneurons were identified using tdTomato-expressing reporter mice and verified through their intrinsic properties in response to hyperpolarizing and depolarizing current injection (see Methods) ( Figure 1B-D ). We used current clamp recordings in the absence of inhibitory synaptic blockers, as opposed to voltage clamp recordings, to more closely mirror the natural physiological activity of striatal circuitry in response to S1 or M1 inputs. Activation of ChR2-expressing S1 corticostriatal afferents with a single, full-field light pulse (2.5 ms, 460-500 nm; through the 40x microscope objective) induced a depolarizing postsynaptic potential (PSP) in D1-SPNs, D2-SPNs and PV interneurons ( Figure 1E-G ). PSP amplitude was larger in PV interneurons (12.81 ± 2.37 mV, n = 9 neurons from 8 mice) compared to D1-SPNs (2.73 ± 0.71 mV, n = 17 neurons from 10 mice, p = 0.000008) or D2-SPNs (3.23 ± 0.95 mV, n = 10 neurons from 6 mice, p = 0.0001) (F (2, 33) = 17.64, p = 0.000006; Figure 1H ). Suprathreshold responses were sometimes encountered in PV interneurons, but only rarely in D1-or D2-SPNs. Measurable PSPs were found in all recorded neurons, suggesting that S1 innervates D1-, D2-SPNs and PV interneurons with high probability, but tha...

The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and is considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in the strength of their connections with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS, and as a result exert an opposing influence on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution onto striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1, and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex-vivo patch-clamp electrophysiology. We found that SPNs are less innervated by S1 compared to M1, but FSIs receive a similar number of inputs from both M1 and S1. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPNs and FSIs. Notably, clusters of inputs were prevalent in SPNs but not FSIs. Our results suggest that SPNs have stronger functional connectivity to M1 compared to S1 due to a higher density of synaptic inputs. The clustering of M1 and S1 inputs onto SPNs but not FSIs suggest that cortical inputs are integrated through cell-type specific mechanisms and more generally have implications for how sensorimotor integration is performed in the striatum.