HABITUATION AND SENSITIZATION OF THE MONOSYNAPTIC REFLEX IN IN VITRO SPINAL CORD

The capacity to ignore only those stimuli that are irrelevant and to channel behaviour into organized and directed actions in response to meaningful stimuli is necessary to conserve energy and focus behaviour. This behavioural definition of habituation and sensitization allows to understand the important role played by the two simplest forms of non-associative learning in ordinary life. Likely habituation and sensitization are terms denoting different neural processes (depression and facilitation) which work and compete each other, determining the final behaviour. The complexity of the mammalian models used to study habituation and sensitization 1,2 did not clarify the underlain mechanisms of these processes. They have been studied also in invertebrate models at a cellular level but the obtained results did not exhaustive explain these processes in mammalians. This study was aimed to use the monosynaptic pathway in in vitro spinal cord preparation of rat as a new model to study learning processes in mammalian. Furthermore we investigated how the two opposite processes of habituation and sensitization can interact to shape the final behavioural outcome. The spinal cord preparation has been isolated from rats between 5 and 15 days old. The dorsal root has been stimulated and the homologue MVR has been recorded. The MVR amplitude has been used as a parameter to evaluate the learning process. Repetitive application of a test stimulus (low intensity/low frequency stimulus, TS) resulted in an exponential decrement of the response, followed by its spontaneous recovery when the stimulation was withheld. The depression was directly related to the stimulus frequency and inverse related to the stimulus intensity. Furthermore habituation of the response occurred faster an at higher degree when more than one training trails have been used (potentiation of habituation). Its spontaneous recovery was longer when the final plateau-like level was reached and further stimuli were delivered (below zero effect). On the contrary a facilitation of the MVR was seen when a strong, noxious stimulus (high intensity stimulus, CS) was applied to a flexor root and the MVR was elicited from a different flexor root (dishabituation). The facilitatory effect of the CS decreased if it was repetitively applied (habituation of dishabituation). Interestingly an additional depression appeared on the habituated response, when the CS was delivered from a flexor root and the MVR was evoke from an extensor root. The stimulus features played a rule in elicit depression or facilitation. It was possible to elicit a pure depression and a pure facilitation processes, described by a simple mathematical model. A repeated stimulation could result in a depression of the response. However if the stimulus was sufficiently strong depression could be preceded by a transient facilitation or even replaced by enduring sensitization. The central processes underlain habituation and sensitization must to be inferred (Kandel, 1973). A decrement to repeated stimulation is usually termed habituation if it exhibits properties consistent with the behavioural definition of habituation. The MVR showed all the features of behavioural habituation, indicates by Rankin and colleagues (Rankin et all., 2009). The parameters of the TS and the CS could be modified to study the complex interactions between these two processes. Lastly this study represents an additional proof for the dual process theory of learning in which the two opposite processes interact to shape the final behaviour. In conclusion, the possibility to stimulate the dorsal roots with a well-known and defined input (the stimulation), to record the activity of the final output of the motoneurons (the behaviour) and to gain access to the cells underlain this circuit in a very well controlled conditions (known solutions, temperature, possibility to use drugs, etc.), give us the opportunity to use the in vitro spinal cord preparation of rat as a good model to study learning and memory in mammalian nervous system.