Cerebellar Purkinje cell responses to afferent inputs. I. Climbing fiber activation (original) (raw)

Clusters of cerebellar Purkinje cells control their afferent climbing fiber discharge

Proceedings of the National Academy of Sciences of the United States of America, 2013

Climbing fibers, the projections from the inferior olive to the cerebellar cortex, carry sensorimotor error and clock signals that trigger motor learning by controlling cerebellar Purkinje cell synaptic plasticity and discharge. Purkinje cells target the deep cerebellar nuclei, which are the output of the cerebellum and include an inhibitory GABAergic projection to the inferior olive. This pathway identifies a potential closed loop in the olivo-cortico-nuclear network. Therefore, sets of Purkinje cells may phasically control their own climbing fiber afferents. Here, using in vitro and in vivo recordings, we describe a genetically modified mouse model that allows the specific optogenetic control of Purkinje cell discharge. Tetrode recordings in the cerebellar nuclei demonstrate that focal stimulations of Purkinje cells strongly inhibit spatially restricted sets of cerebellar nuclear neurons. Strikingly, such stimulations trigger delayed climbing-fiber input signals in the stimulated Purkinje cells. Therefore, our results demonstrate that Purkinje cells phasically control the discharge of their own olivary afferents and thus might participate in the regulation of cerebellar motor learning. motor control | olivo-cerebellar loop | complex spikes T he cerebellar cortex is involved in a wealth of functions, from the control of posture to higher cognitive processes (1-3). Purkinje cells (PCs) are key processing units of the cerebellar cortex (4): each PC receives more than 175,000 parallel fiber synaptic inputs carrying information about the ongoing sensorymotor context. It also receives a single inferior olive afferent, the climbing fiber, which triggers a complex spike (CS), modulates PC firing (5), controls synaptic input plasticity, and has been proposed to carry error and clock signals to the cerebellum (2, 4-8). PCs are grouped in multiple parasagittal microzones, each receiving projections from separate areas of the inferior olive and projecting to subregions of the cerebellar nuclei (CN) (9-12). In the CN, PCs make inhibitory contacts on excitatory neurons that project to various premotor areas and propagate cerebellar computations to the motor system. Anatomical evidence indicates that PC terminals also contact CN inhibitory neurons that target inferior olive cells . This nucleoolivary pathway is topographically organized in multiple parallel projections to the inferior olive subnuclei (15), suggesting the existence of closed olivary-cortico-nuclear loops. Therefore, the discharge of a population of PCs in a microzone might not only shape the output of the cerebellum but also control its afferent climbing-fiber signal. Previous studies have shown that stimulation of the nucleo-olivary pathway significantly reduces olivary cell firing (16-18) and that pharmacological and genetic manipulations of PCs or olivary cell activity induce reciprocal modulations of the firing rate of PCs and climbing fibers .

Repetitive firing of cerebellar Purkinje cells in response to impulses in climbing fibre afferents

Neuroscience Letters, 1981

The effects of climbing fibre (CF) impulses on the discharges of cerebellar cortical cells has been studied in the cat. It was found that a brief burst of impulses in a CF can evoke a prolonged excitatory response in the Purkinje (P) cell it innervates. The response consisted of a burst of action potentials that lasted from 50 to 400 msec in different P cells. Bursts of CF impulses were not observed to accelerate the discharges of granule ceils. It is therefore suggested that this powerful response results from a direct action of CF impulses on the P cell.

Evidence that Climbing Fibers Control an Intrinsic Spike Generator in Cerebellar Purkinje Cells

Journal of Neuroscience, 2004

It is well established that the climbing fiber (CF) input to a cerebellar Purkinje cell (PC) can exert a controlling influence on the background simple spike (SS) activity of the cell, in that repetitive stimulation of CFs causes a decrease in SS activity, and removal or inactivation of CFs is followed by a rise in activity. In the present study, the effects of inactivation of CFs in the short term and longer term (hours) were investigated in anesthetized rats to determine how the CFs control the PC SS activity. Inactivation of the CF input to a PC was accomplished by either reversibly inactivating with lignocaine or by microlesioning the inferior olive. Consistent with previous findings, CF removal caused a transformation of the PC firing pattern, with SSs discharging more regularly and rising to an exceptionally high level. In cases in which CF activity resumed, SS rate declined to control levels within a few seconds. However, with sustained CF inactivation (30 min to 5 hr), SS activity continues to rise progressively and develops an oscillating firing pattern, consisting of alternating bursts of high-frequency discharge at up to 100-150 Hz followed by 10-20 sec periods of electrical quiescence. No accompanying changes in the threshold for evoking SSs via the parallel fibers were seen to accompany the increases in tonic SS activity. We conclude that the increase in SS activity that follows CF inactivation could be caused by the removal of an inhibitory action that CFs exert on the intrinsic pacemaker present in PCs under normal conditions.