Date of Award
Doctor of Philosophy
One of the best understood models of motor learning is the eyeblink classical conditioning paradigm in rabbits. Eyeblink conditioning relies on cerebellar circuits for the generation and expression of conditioned responses (CRs). Although these circuits have been studied extensively, their specific function is unknown and highly debated. To this end, a series of experiments were conducted to gain insight into the role of the intermediate cerebellum in the timing and retention of CRs.
The first objective of our research was to develop an accurate method to record rabbit eyeblinks. We developed an infrared, frequency modulated, non-invasive sensor with a wide-field of view. The sensor was tested against previous opto-electric, electromechanical, and video recording systems and as a result of its accuracy in eyeblink detection, this sensor was used in all subsequent experiments.
In the first group of neuropharmacological experiments, we examined the effects of inactivating the cerebellar cortical GABAergic Purkinje cell projection to the interposed nuclei (IN) on CR expression. This study successfully reconciled a long-standing controversy by documenting the dose-dependency of behavioral effects. While low doses of GABAergic blockers shortened CR latencies (short-latency responses - SLRs), the high doses of these drugs abolished CRs. In addition, low doses of GABA blockers facilitated the expression of unconditioned eyeblinks and increased eyelid closure. These data indicate that CR timing is altered only during an incomplete block of the cortical projections to the IN and that the intermediate cerebellum controls non-associative components of blinking.
The next group of experiments examined whether SLRs are triggered by cerebellum-mediated sensory information. To address this question, we inactivated the conditioned stimulus (CS)-carrying axons in the middle cerebellar peduncle (MCP) in rabbits producing SLRs. We found that blocking CS information from entering the intermediate cerebellum does in fact abolish both CRs and SLRs. This finding suggests that SLRs are cerebellum-dependent responses that are evoked by residual CS information entering the cerebellum via incompletely blocked cortical projections to the nuclei.
In the last group of experiments we tested whether the behavioral effects of MCP inactivation could be attributed to a tonic malfunction of cerebellar circuits. Classically conditioned rabbits were injected with sodium channel blocker tetrodotoxin (TTX) in the MCP while recording from cells in the interposed nuclei (IN). This treatment abolished CRs and elevated the spontaneous activity of IN neurons. Surprisingly, the CS-related modulation was not blocked and in some cases it increased. These observations suggest that normal functioning of the MCP is critical for CR expression, and the persistence of CS-related IN activity indicates that a significant portion of CS information reaches the cerebellum through pathways other than the ipsilateral MCP.
Krystal Lynn Parker
Parker, Krystal Lynn, "The role of cerebellar nuclear GABAergic neurotransmission in eyeblink motor control" (2009). Graduate Theses and Dissertations. 10509.