Protecciones IP e IK

An alternative to learning-related plasticity being confined to the cerebellar cortex or cerebellar nuclei is that NMR conditioning might involve plasticity in both regions. If so, how does each structure contribute to the learning? Is the plasticity distributed

equally among the two loci throughout conditioning or are distinct functions served by each during learning?

The vestibular ocular reflex (VOR) has some similarities with eyeblink conditioning. Both forms o f learning require paired stimulus presentations. In the VOR, learning occurs following pairings o f head rotation with image motion. In eyeblink conditioning, learning can occur with pairings o f a tone and periocular stimulus. Another similarity between VOR adaptation and eyeblink conditioning is the debate that surrounds essential plasticity. VOR adaptation is critically dependent on the cerebellar cortex and vestibular nuclei (see Ito, 1998), and it is not resolved whether essential plasticity resides in one or both structures. Ito (1982) suggests that VOR adaptation involves a reduction in strength o f the parallel fibre to Purkinje cell synapse, whereas others propose that VOR adaptation also involves modifications in the vestibular inputs to cells in the vestibular nucleus (see Raymond et al, 1996).

Similar analyses have been applied to eyeblink conditioning. A dual locus model for eyelid conditioning has been proposed (Mauk, 1997; Mauk and Donegan, 1997). It is suggested that conditioned responses are mediated by plasticity in the cerebellar cortex and in the cerebellar nuelei. Learning is proposed to occur first in the cortex and then it is transferred to the nucleus. Induction o f plasticity in the nucleus is controlled by plasticity in the cerebellar cortex, and both forms o f plasticity can undergo LTP and LTD. In this model, granule eell/Purkinje cell synapses undergo LTD when active in the presence o f a climbing fibre input, but they increase in strength (LTP) when active without the climbing fibre input. The plasticity at the mossy fibre/interpositus synapse is dependent on the inhibitory Purkinje cell input. The mossy fibre/interpositus nucleus synapse undergoes a form o f Hebbian plasticity when it is active during transient decreases in Purkinje cell activity, but they decrease in strength when active in the presence o f a strong inhibitory Purkinje cell input. In this model, conditioned responses result from increased synaptic activation o f the interpositus and decreased inhibition o f the interpositus through LTD in the cerebellar cortex. It is suggested that extinction learning involves the complete reversal o f plasticity responsible for the acquisition o f CRs. In this case, there is potentiation o f the granule cell to Purkinje cell synapses and depression o f the mossy fibre to interpositus synapses.

In the model proposed by Mauk, it is argued that sinee response timing in classieal conditioning is learned, it must involve some additional form o f synaptic plasticity, separable from general response expression. It is suggested that the cerebellar cortex is necessary for the learned timing o f the CR and the cerebellar nuelei support the expression o f conditioned eyelid responses. Evidence supporting the dual locus, expression/timing model is rather weak. It is claimed that lesions o f the anterior lobe of the cerebellar cortex spare conditioned eyelid responses, but disrupt response timing, revealing short latency responses (Perrett et al, 1993, Perrett and Mauk, 1995; Garcia et al, 1998). A disruption in response timing following such lesions is regarded as evidence consistent with separate mechanisms o f response timing and response expression. However, a major concern about the short latency responses seen after cerebellar cortical lesions is that they might not be assoeiatively produced conditioned responses, but represent non-associative, sensitised responses to the auditory stimulus that are unmasked by the disinhibitory cortical lesions.

One assumption in the model proposed by Mauk is that mossy fibre collaterals to the AIP are sufficient for conditioned response expression. But the mossy fibre projections from the pontine nuclei to the cerebellar nuclei are sparse (Brodai & Bjaalie, 1992) and there is no evidence to suggest that they can activate movements. Strong stimulation o f the MCP, which mainly activates pontine mossy fibres, would be expected to excite neurones from the AIP nucleus and cerebellar cortex, and potentially produce short latency and long latency eyelid EMG activity respectively (Hesslow et al, 1999). Analysis o f conditioned response latencies evoked by MCP stimulation however reveals no short latency responses, suggesting that CRs are generated by pontine mossy fibre projections through the cerebellar cortex.

Another possible, but indirect mechanism for learning in the AIP is an association between the inhibitory cerebellar cortical input and climbing fibre input to the AIP, whereby CS related information can be transmitted to the AIP via the cerebellar cortex, thus eliminating the need o f pontine nuelei mossy fibre collaterals to the AIP. This mechanism for learning within the AIP might be with or without cerebellar cortical plasticity. Consistent with this hypothesis, LTD and LTP have been reported between the Purkinje cell - cerebellar nuclear synapse (Aizenman et al, 1998).

Is memory stored in the same region that changes during learning? One possibility is that the primary site o f change reverts to the original state, and the modifications are stored in another part o f the brain. For instance, since the cerebellar cortex receives appropriate converging inputs, the learning related modifications might take place in the cortex, but then are subsequently transferred and stored in the cerebellar nuclei. This would eliminate the need o f appropriate converging inputs to the nuclei.