Mammalian cerebral cortex is accepted as being critical for voluntary motor control, but what functions depend on cortex is still unclear. Here we used rapid, reversible optogenetic inhibition to test the role of cortex during a head-fixed task in which mice reach, grab, and eat a food pellet. Sudden cortical inhibition blocked initiation or froze execution of this skilled prehension behavior, but left untrained forelimb movements unaffected. Unexpectedly, kinematically normal prehension occurred immediately after cortical inhibition, even during rest periods lacking cue and pellet. This ‘rebound’ prehension was only evoked in trained and food-deprived animals, suggesting that a motivation-gated motor engram sufficient to evoke prehension is activated at inhibition’s end. These results demonstrate the necessity and sufficiency of cortical activity for enacting a learned skill.DOI: http://dx.doi.org/10.7554/eLife.10774.001

Motor cortex controls skilled arm movement by sending temporal patterns of activity to lower motor centers 1. Local cortical dynamics are thought to shape these patterns throughout movement execution 2-4. External inputs have been implicated in setting the initial state of motor cortex 5,6 , but they may also have a pattern-generating role. Here, we dissect the contribution of local dynamics and inputs to cortical pattern generation during a prehension task in mice. Perturbing cortex to an aberrant state prevented movement initiation, but after the perturbation was released, cortex either bypassed the normal initial state and immediately generated the pattern that controls reaching, or it failed to generate this pattern. The difference in these two outcomes was likely due to external inputs. We directly investigated the role of inputs by inactivating thalamus; this perturbed cortical activity and disrupted limb kinematics at any stage of the movement. Activation of thalamocortical axon terminals at different frequencies disrupted cortical activity and arm movement in a graded manner. Simultaneous recordings revealed that both thalamic activity and the current state of cortex predicted changes in cortical activity. Thus, the pattern generator for dexterous arm movement is distributed across multiple, strongly-interacting brain regions. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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The functional role of nicotinic acetylcholine receptors (nAChRs) in the ventral lateral geniculate nucleus (LGNv) was examined in chick brain slices. Whole-cell patch-clamp recordings of neurons in the LGNv revealed the presence of bicuculline-resistant spontaneous postsynaptic currents (PSCs), which were subsequently blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an AMPA receptor antagonist. Carbachol and other nicotinic agonists produced marked increases in the frequency of the glutamatergic spontaneous PSCs in the presence of tetrodotoxin, whereas they had little or no effect on current amplitude. The nicotinic receptor antagonist dihydro-beta-erythroidine (DHbetaE) blocked the carbachol-induced enhancement of spontaneous glutamatergic PSCs. alpha-bungarotoxin (alpha-BgTx) selectively blocked the nAChR-mediated enhancement of spontaneous glutamatergic PSCs but did not prevent nAChR-mediated enhancement of spontaneous GABAergic PSCs in the LGNv. Methyllycaconitine and strychnine, other blockers of nAChRs containing the alpha7 subunit, failed to inhibit carbachol's increase of spontaneous glutamatergic and GABAergic PSCs. These results demonstrate that the LGNv neurons receive both glutamatergic and GABAergic inputs and that the release of these transmitters can be modulated by different presynaptic nAChRs. Thus, the regulation of synaptic efficacy in the brain by presynaptic nAChRs can be complex, involving multiple neurotransmitters acting on the same neuron.