Sensory Stimulation-Dependent Plasticity in the Cerebellar Cortex of Alert Mice

In vitro studies have supported the occurrence of cerebellar long-term depression (LTD), an interaction between the parallel fibers and Purkinje cells (PCs) that requires the combined activation of the parallel and climbing fibers. To demonstrate the existence of LTD in alert animals, we investigated the plasticity of local field potentials (LFPs) evoked by electrical stimulation of the whisker pad. The recorded LFP showed two major negative waves corresponding to trigeminal (broken into the N2 and N3 components) and cortical responses. PC unitary extracellular recording showed that N2 and N3 occurred concurrently with PC evoked simple spikes, followed by an evoked complex spike. Polarity inversion of the N3 component at the PC level and N3 amplitude reduction after electrical stimulation of the parallel fiber volley applied on the surface of the cerebellum 2 ms earlier strongly suggest that N3 was related to the parallel fiber–PC synapse activity. LFP measurements elicited by single whisker pad stimulus were performed before and after trains of electrical stimuli given at a frequency of 8 Hz for 10 min. We demonstrated that during this later situation, the stimulation of the PC by parallel and climbing fibers was reinforced. After 8-Hz stimulation, we observed long-term modifications (lasting at least 30 min) characterized by a specific decrease of the N3 amplitude accompanied by an increase of the N2 and N3 latency peaks. These plastic modifications indicated the existence of cerebellar LTD in alert animals involving both timing and synaptic modulations. These results corroborate the idea that LTD may underlie basic physiological functions related to calcium-dependent synaptic plasticity in the cerebellum

Electrophysiological Characterization of The Cerebellum in the Arterially Perfused Hindbrain and Upper Body of The Rat

In the present study, a non-pulsatile arterially perfused hindbrain and upper body rat preparation is described which is an extension of the brainstem preparation reported by Potts et al., (Brain Res Bull 53(1):59–67), 1. The modified in situ preparation allows study of cerebellar function whilst preserving the integrity of many of its interconnections with the brainstem, upper spinal cord and the peripheral nervous system of the head and forelimbs. Evoked mossy fibre, climbing fibre and parallel fibre field potentials and EMG activity elicited in forelimb biceps muscle by interpositus stimulation provided evidence that both cerebellar inputs and outputs remain operational in this preparation. Similarly, the spontaneous and evoked single unit activity of Purkinje cells, putative Golgi cells, molecular interneurones and cerebellar nuclear neurones was similar to activity patterns reported in vivo. The advantages of the preparation include the ability to record, without the complications of anaesthesia, stabile single unit activity for extended periods (3 h or more), from regions of the rat cerebellum that are difficult to access in vivo. The preparation should therefore be a useful adjunct to in vitro and in vivo studies of neural circuits underlying cerebellar contributions to movement control and motor learning

Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation

Long-term potentiation (LTP) in the rat hippocampus is the most extensively studied cellular model for learning and memory. Induction of classical LTP involves an NMDA receptor- and calcium-dependent increase in functional synaptic AMPA receptors mediated by enhanced recycling of internalized AMPA receptors back to the postsynaptic membrane. Here we report a novel, physiologically relevant NMDA receptor-independent mechanism that drives increased AMPA receptor recycling and LTP. This pathway requires the metabotropic action of kainate receptors and activation of G-protein, protein kinase C and phospholipase C. Like classical LTP, kainate receptor-dependent LTP recruits recycling endosomes to spines, enhances synaptic recycling of AMPA receptors to increase their surface expression and elicits structural changes in spines, including increased growth and maturation. These data reveal a new and previously unsuspected role for postsynaptic kainate receptors in the induction of functional and structural plasticity in the hippocampus

Acteurs du littoral : usages, organisations et modes de gestion d'un espace naturel et de ses ressources

rapport final (contrat MAPAR), éd. IFRESI, Lill

Protein tyrosine kinase is required for the induction of long-term potentiation in the rat hippocampus

Protein tyrosine phosphorylation is thought to play an important role in the regulation of neuronal function. Previous work has shown that protein tyrosine kinase (PTK) inhibitors can inhibit the induction of long-term potentiation (LTP), a candidate synaptic mechanism involved in memory formation. However, how PTK activity might contribute to LTP induction remains elusive. To understand the role of PTK pathways in the development of LTP better, a set of studies was implemented in area CA1 of rat hippocampal slices using both intra- and extracellular recordings. We show here that bath application or injection into postsynaptic cells of the PTK inhibitors genistein and lavendustin A blocked the induction of LTP produced by high-frequency tetanic stimulation.Application of lavendustin A 10 min before or 3 min after induction effectively blocked LTP. However, application at 10 or 30 min after induction had no detectable effect on potentiation.PTK inhibitor pretreatment did not affect the long-lasting enhancement of synaptic response produced by phorbol 12,13-dibutyrate (PDBu), forskolin plus 3-isobutyl-L-methylxanthine (IBMX), or tetraethylammonium (TEA). In contrast, PTK inhibitors significantly blocked postanoxic LTP.EPQ(pY)EEIPIA, an activator of Src family PTKs, produced a gradual and robust increase in the synaptic response and occluded LTP.These results suggest that Src family kinases are potential candidates for the PTKs contributing to the molecular mechanism of LTP induction at Schaffer collateral-CA1 synapses