Synaptic representation of locomotion in single cerebellar granule cells

Abstract

The cerebellum plays a crucial role in the regulation of locomotion, but how movement is represented at the synaptic level is not known. Here, we use in vivo patch-clamp recordings to show that locomotion can be directly read out from mossy fiber synaptic input and spike output in single granule cells. The increase in granule cell spiking during locomotion is enhanced by glutamate spillover currents recruited during movement. Surprisingly, the entire step sequence can be predicted from input EPSCs and output spikes of a single granule cell, suggesting that a robust gait code is present already at the cerebellar input layer and transmitted via the granule cell pathway to downstream Purkinje cells. Thus, synaptic input delivers remarkably rich information to single neurons during locomotion.DOI: http://dx.doi.org/10.7554/eLife.07290.001

Heterosynaptic GABAergic plasticity bidirectionally driven by the activity of pre- and postsynaptic NMDA receptors

“…Recent findings also showed that when sensory information is conveyed to GrCs, the temporal precision of excitatory neurotransmission is weakened by GoC synaptic inhibition in favor of an increased response reproducibility across the GrC population (11). Our results demonstrate that the excess of excitation generated by LTP glu in poorly inhibited GrCs is compensated by LTP GABA improving time windowing (4).…”

“…The GoC-mediated inhibition is a fundamental player in controlling the temporal coding in cerebellar circuitry. GoC inhibition was in fact shown to operate as gain controller of GrC excitation and regulator of the temporal fidelity of mf-GrC neurotransmission (11,15,17,35).…”

“…The cerebellum coordinates sensory-motor function via the firing patterns of Purkinje cells (PCs), which are in turn modulated by the granular layer activity. Recent findings highlighted the role of single granule cells (GrCs) in processing cerebellar signals during locomotion, motor coordination, and sensory-motor integration (11,12). Furthermore, the local computation in the granular layer is under control of Golgi cell (GoC) inhibitory activity through feedback and feedforward loops (13).…”

Resistance to action potential depression of a rat axon terminal in vivo

“…Following the AP, the membrane potential during the recovery period has a large influence on the speed of the recovery from inactivation of voltage-dependent sodium channels and deactivation of voltagedependent potassium channels, which are two major determinants of the refractory period (2). In some terminals, the AP is followed by a depolarizing afterpotential (DAP) (3)(4)(5)(6)(7)(8)(9), whereas in others a hyperpolarizing afterpotential (HAP) has been observed (10)(11)(12)(13)(14). The sign of this afterpotential depends on the resting potential (6,7,15), suggesting that the membrane potential following the AP (V after ) might be more important than the sign of the afterpotential.…”

“…In slice studies, a large DAP has been observed (3), to which resurgent sodium currents (23) make a prominent contribution, and which may promote high-frequency firing (15). With the exception of cerebellar mossy fiber terminals (4,8), studies on the biophysical properties of mammalian presynaptic terminals have been performed ex vivo, and the functional significance of afterpotentials, including their role during natural firing patterns, is currently largely unknown. Here, we make in vivo juxtacellular and whole-cell recordings from the calyx of Held in rat pups, and study how the afterpotentials contribute to the stability of presynaptic APs during natural firing patterns.…”