Neocortical activity can evoke sensory percepts, but the cellular mechanisms remain poorly understood. We trained mice to detect single brief whisker stimuli and report perceived stimuli by licking to obtain a reward. Pharmacological inactivation and optogenetic stimulation demonstrated a causal role for the primary somatosensory barrel cortex. Whole-cell recordings from barrel cortex neurons revealed membrane potential correlates of sensory perception. Sensory responses depended strongly on prestimulus cortical state, but both slow-wave and desynchronized cortical states were compatible with task performance. Whisker deflection evoked an early (<50 ms) reliable sensory response that was encoded through cell-specific reversal potentials. A secondary late (50-400 ms) depolarization was enhanced on hit trials compared to misses. Optogenetic inactivation revealed a causal role for late excitation. Our data reveal dynamic processing in the sensory cortex during task performance, with an early sensory response reliably encoding the stimulus and later secondary activity contributing to driving the subjective percept.

Endocannabinoids act as retrograde signals to modulate synaptic transmission. Little is known, however, about their significance in integrated network activity underlying motor behavior. We have examined the physiological effects of endocannabinoids in a neuronal network underlying locomotor behavior using the isolated lamprey spinal cord. Our results show that endocannabinoids are released during locomotor activity and participate in setting the baseline burst rate. They are released in response to mGluR1 activation and act as retrograde messengers. This conditional release of endocannabinoids can transform motoneurons and crossing interneurons into modulatory neurons by enabling them to regulate their inhibitory synaptic inputs and thus contribute to the modulation of the locomotor burst frequency. These results provide evidence that endocannabinoid retrograde signaling occurs within the locomotor network and contributes to motor pattern generation and regulation in the spinal cord.

Retrograde signaling by endocannabinoids is known to induce short-and long-term synaptic plasticity, but the significance of this modulation for the activity of neural networks underlying motor behavior is largely unclear. Here, we used the isolated lamprey spinal cord to show that endocannabinoids released by activation of metabotropic glutamate receptor 1 (mGluR1) induce long-term synaptic plasticity during an ongoing locomotor rhythm and how this is translated onto the integrated activity of the spinal circuitry. A brief activation of mGluR1 induces a long-term increase in the locomotor frequency that is mediated by a concomitant long-term depression of midcycle reciprocal inhibition and long-term potentiation of ipsilateral synaptic excitation arising from locomotor circuit interneurons. Blockade of cannabinoid receptors with AM251 prevented the mGluR1-mediated long-term plasticity of both inhibitory and excitatory synaptic transmission, as well as that of the locomotor activity. Similarly, inhibition of nitric oxide signaling blocked the mGluR1-mediated long-term plasticity. These results show that the locomotor circuitry is endowed with a "memory" capacity mediated by a long-term shift in the balance between synaptic inhibition and excitation. This is triggered by activation of mGluR1 and requires subsequent endocannabinoid and nitric oxide signaling.

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Motor behavior is generated by specific neural circuits. Those producing locomotion are located in the spinal cord, and their activation depends on descending inputs from the brain or on sensory inputs. In this study, we have used an in vitro brainstem-spinal cord preparation from adult zebrafish to localize a region where stimulation of descending inputs can induce sustained locomotor activity. We show that a brief stimulation of descending inputs at the junction between the brainstem and spinal cord induces long-lasting swimming activity. The swimming frequencies induced are remarkably similar to those observed in freely moving adult fish, arguing that the induced locomotor episode is highly physiological. The motor pattern is mediated by activation of ionotropic glutamate and glycine receptors in the spinal cord and is not the result of synaptic interactions between neurons at the site of the stimulation in the brainstem. We also compared the activity of motoneurons during locomotor activity induced by electrical stimulation of descending inputs and by exogenously applied NMDA. Prolonged NMDA application changes the shape of the synaptic drive and action potentials in motoneurons. When escape activity occurs, the swimming activity in the intact zebrafish was interrupted and some of the motoneurons involved became inhibited in vitro. Thus, the descending inputs seem to act as a switch to turn on the activity of the spinal locomotor network in the caudal spinal cord. We propose that recurrent synaptic activity within the spinal locomotor circuits can transform a brief input into a well coordinated and long-lasting swimming pattern.