Aim: 

The nAChRs play an important role in regulating neuronal synaptic transmission and plasticity in various brain regions (Wannacott, 1997) and are implicated in major brain pathologies. Although nAChRs are found in the cerebellum, their functional effects are still largely unknown.

Methods: 

We have performed voltage-clamp recordings in whole-cell configuration in the granular layer of acute slices obtained from the cerebellar vermis and in vivo extracellular field recordings in the cerebellar cortex Crus IIa of P18-P23 rats. Moreover, to evaluate [Ca²⁺] dynamics we have carried out experiments combining voltage-clamp and fluorescence Ca²⁺ imaging techniques.

Results: 

A brief application (100 sec) of nicotine (1 ?M) or choline (10 mM), a selective alfa-7 receptor agonist, increased the EPSCs and reduced the paired-pulse ration (PPR) suggesting a presynaptic effect. However, contrary to a pure presynaptic effect, the NMDA EPSC did not show any significant increase. A postsynaptic effect was indeed indicated by the action of BAPTA perfusion into the postsynaptic neuron, which revealed a potentiating effect of nicotine on the NMDA component. This result could be explained by assuming that nicotine increased postsynaptic Ca²⁺ causing NMDA receptor desensitization. Indeed, Ca²⁺ imaging experiments showed that postsynaptic Ca²⁺ elevationselicited by short mossy fiber bursts increased more markedlywhen choline (10 mM) was perfused. Interestingly, nicotine or choline application lowered the threshold for LTP induction. A single 100ms/100Hz burst, which would normally evoke long-term depression (Maffei et al., 2003; Gall et al., 2005), induced LTP when applied in the presence of nicotine or choline. The co- application of nicotine with MLA (10 nM), an the alfa-7 receptor antagonist, prevented switching form LTD to LTP. Similar results were obtained in vivo. The response to tactile facial stimulation was enhanced in the presence of nicotine or choline. Moreover, a theta-sensory stimulus (TSS) induced LTP in the presence of nicotine or choline, while the same caused LTD in the presence of MLA.

Conclusions: 

These results suggest that cholinergic stimulation mediated by ?7-nAChRs markedly potentiates synaptic transmission and LTP at the mossy fibre – granule cell relay of cerebellum both in vitro and in vivo, providing a powerful gating mechanism for learning at the cerebellum input stage.

References: 

Wonnacott S (1997) Presynaptic nicotinic ACh receptors Trends Neurosci 20: 92-8.

Maffei A, Prestori F, Rossi P,Taglietti V, D'Angelo E (2003) Presynaptic current changes at the mossy fiber-granule cell synapse of cerebellum during LTP. J Neurophysiol 88:627-638.

Gall D, Prestori F, Sola E, D'Errico A, Roussel C, Forti L, Rossi P, D'Angelo E (2005) Intracellular calcium regulation by burst discharge determines bidirectional long-term synaptic plasticity at the cerebellum input stage. J Neurosci 4813-4822.