Plasticity of the olivocerebellar pathway

Learning motor skills is critical for motor abilities such as driving a car or playing piano. The speed at which we learn those skills is subject to many factors. Yet, it is not known to what extent gonadal hormones can affect the achievement of accurate movements in time and space. Here we demonstrate via different lines of evidence that estradiol promotes plasticity in the cerebellar cortex underlying motor learning. First, we show that estradiol enhances induction of long-term potentiation at the parallel fiber to Purkinje cell synapse, whereas it does not affect long-term depression; second, we show that estradiol activation of estrogen receptor ␤ receptors in Purkinje cells significantly improves gain-decrease adaptation of the vestibulo-ocular reflex, whereas it does not affect general eye movement performance; and third, we show that estradiol increases the density of parallel fiber to Purkinje cell synapses, whereas it does not affect the density of climbing fiber synapses. We conclude that estradiol can improve motor skills by potentiating cerebellar plasticity and synapse formation. These processes may be advantageous during periods of high estradiol levels of the estrous cycle or pregnancy.

Section: Discussionmentioning

confidence: 99%

Estradiol Improves Cerebellar Memory Formation by Activating Estrogen Receptor β

Andreescu¹,

Milojkovic²,

Haasdijk³

et al. 2007

“…The spiny dendrites of mormyrid Purkinje cells are equivalent to the spiny branchlets of mammalian Purkinje cells. In the mammalian cerebellum, PFs contact spines on the spiny branchlets, whereas the CF input contacts spines that occur at low density on the primary, secondary, and tertiary dendrites from which the spiny branchlets arise (Larramendi and Victor, 1967;Strata and Rossi, 1998). Thus, in both the mormyrid and the mammalian cerebellum, the PF and CF input territories do not overlap, but in mormyrid Purkinje cells, the separation between the CF input and distal PF inputs is more pronounced.…”

Section: Introductionmentioning

confidence: 99%

Synaptic Plasticity and Calcium Signaling in Purkinje Cells of the Central Cerebellar Lobes of Mormyrid Fish

Han

Zhang²,

Bell³

et al. 2007

Climbing fiber (CF)-evoked calcium transients play a key role in plasticity at parallel fiber (PF) to Purkinje cell synapses in the mammalian cerebellum. Whereas PF activation alone causes long-term potentiation (LTP), coactivation of the heterosynaptic CF input, which evokes large dendritic calcium transients, induces long-term depression (LTD). This unique type of heterosynaptic interaction is a hallmark feature of synaptic plasticity in mammalian Purkinje cells. Purkinje cells in the cerebellum of mormyrid electric fish are characterized by a different architecture of their dendritic trees and by a more pronounced separation of CF and PF synaptic contact sites. We therefore examined the conditions for bidirectional plasticity at PF synapses onto Purkinje cells in the mormyrid cerebellum in vitro. PF stimulation at elevated frequencies induces LTP, whereas LTD results from PF stimulation at enhanced intensities and depends on dendritic calcium influx and metabotropic glutamate receptor type 1 activation. LTD can also be observed after pairing of low intensity PF stimulation with CF stimulation. Using a combination of whole-cell patch-clamp recordings and fluorometric calcium imaging, we characterized calcium transients in Purkinje cell dendrites. CF activation elicits calcium transients not only within the CF input territory (smooth proximal dendrites) but also within the PF input territory (spiny palisade dendrites). Paired PF and CF activation elicits larger calcium transients than stimulation of either input alone. A major source for dendritic calcium signaling is provided by P/Q-type calcium channels. Our data show that despite the spatial separation between the two inputs CF activity facilitates LTD induction at PF synapses.

“…Each Purkinje cell receives ϳ100,000 synapses (in the mouse) from small unmyelinated parallel fibers that are the axons of cerebellar granule cells and run normal to the plane of the Purkinje cell dendrite . In marked contrast, each Purkinje cell is said to be innervated by a single climbing fiber (CF) axon, originating in the inferior olive, and elaborating ϳ1400 release sites (Strata and Rossi, 1998) (measured in the rat). Although each Purkinje cell is multiply-innervated at birth, an activity-dependent regression of supernumerary CFs proceeds, yielding single innervation for most Purkinje cells by postnatal day (P) 21 Lohof et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Differential Maturation of Climbing Fiber Innervation in Cerebellar Vermis

Nishiyama

Linden

2004

Folding of the brain surface is a general morphological adaptation to maximize surface area in a limited cranial volume. Surface folding is present not only in the neocortex but also in the cerebellar cortex. This folding creates subdivisions of the cortical surface: the sulci, the gyri, and the straight bank region, which is interposed. Is cortical folding only the solution to a surface-volume problem or does it also confer functional differences on the subdivisions that are created by this geometry? Here we have used the innervation of Purkinje cells by climbing fibers as a model system to explore potential functional differences. Purkinje cells are innervated by multiple climbing fibers at birth but undergo an activity-dependent refinement, such that by postnatal day (P) 21, most are contacted by a single climbing fiber. Using whole-cell recording from slices of cerebellar vermis derived from juvenile (P18 -25) or adult (P60 -83) mice, we found that significantly more Purkinje cells in the sulcus were innervated by multiple climbing fibers than in the gyrus or bank subdivisions; however, the basic properties of climbing fiber-Purkinje cell EPSCs such as kinetics, amplitude, and paired-pulse ratio were similar across cortical subdivisions. To search for a morphological correlate of differential multiple climbing fiber innervation, we labeled climbing fibers and performed reconstructions of immunofluorescent images. These revealed that, unlike the bank-gyrus subdivisions, most of the climbing fibers in the sulcus do not innervate the superficial molecular layer. These findings suggest that the subdivisions of the cerebellar cortex produced by folding may create functionally distinct entities.