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Biomedical Engineering Program
B.S. 2005, New Jersey Institute of Technology
Thesis Advisor: Kevin C.H. Pang, Ph.D.
Department of Neurology & Neurosciences
Tuesday, May 14, 2013
4:00 P.M., NJIT, Fenster Hall, Room 698
The hippocampal region—composed of fields of the hippocampus, the dentate gyrus, the subiculum, and the entorhinal cortex—has been extensively studied in relation to its involvement in learning and memory processes in both humans and animals. Even though the role of hippocampus itself is well characterized, the function of other hippocampal structures is less clear. Here we are interested in the role of entorhinal cortex in learning and memory processes. Entorhinal cortex is a primary source of polymodal sensory input to the hippocampus and receives highly convergent projections from a wide range of association cortices. It also contains backprojections from hippocampus allowing feedback communication with the same cortices. An important issue is whether entorhinal cortex is an essential contributor to learning processes separate from that contributed by the hippocampus or whether it serves solely as a passive relay of information to the hippocampus. The distinctive anatomical location and organization of the entorhinal cortex is suggestive of its important role in stimulus processing, especially compressing of the cortical information prior to inputting to the hippocampus. In assessing this, we employed the latent inhibition paradigm, an ubiquitous phenomenon occurring in numerous species and in diverse conditioning paradigms. Latent inhibition refers to the retardation in learning of a conditioned stimulus - unconditioned stimulus association following non-reinforced repeated exposure to the conditioned stimulus alone prior to conditioning. Latent inhibition is considered to index the capacity of organisms to ignore stimuli with no predictive significance and consequence and has been classically used as an experimental paradigm to study and model the neurobiological bases of the psychotic disorder schizophrenia.
Here we examined the suggested role of the hippocampal region in latent inhibition in rats by distinguishing the involvement of hippocampus and entorhinal cortex. Results indicated the disruption of delay eyeblink conditioning paradigm of latent inhibition by selective lesions of entorhinal cortex, but not hippocampus. The functional role of the two structures was further differentiated by examining their involvement in a Morris water maze spatial task which revealed performance impairment following hippocampal, but not entorhinal, lesions. This result adds to a growing body of literature indicative of entorhinal cortex as a dynamic information processor, essential to the neurocircuitry of latent inhibition, and functionally distinct from hippocampus, rather than just a simple gateway of information between hippocampus and neocortex.
Entorhinal’s involvement in latent inhibition was further explored by examining the contribution of its two major divisions, the medial entorhinal cortex and the lateral entorhinal cortex. Considering the distinctions in their efferent and afferent projections, the two divisions are suggested to receive and process qualitatively different types of information. Our data concluded the abolition of latent inhibition as result of lateral entorhinal lesions, eliminating the conditioning impairment generally seen as results of pre-exposure to the conditioning stimulus prior to conditioning. In contrast, rats with medial entorhinal lesions continued to show latent inhibition. Our data suggests that the two regions of entorhinal cortex may encode and process different information characteristics in latent inhibition of eyeblink conditioning.
In an attempt to explicate the mechanism by which the entorhinal cortex exerts its impact on latent inhibition, we also examined the involvement of nucleus accumbens in latent inhibition. Nucleus accumbens, a structure of ventral striatum known for its prominent role in the reward and motivation processes, is heavily innervated by entorhinal cortex and is suggested to be a critical component of the neural circuitry underlying latent inhibition. It is proposed that the suppression of latent inhibition observed following entorhinal lesions might be the consequence of the alteration of nucleus accumbens dopaminergic activity induced by the disruption of the entorhino-accumbens pathway. Our results showed that latent inhibition is left intact following nucleus accumbens lesions, suggesting that nucleus accumbens may not be involved in latent inhibition of delay eyeblink conditioning, weakening the assumption that latent inhibition disruption following entorhinal lesions seen before was due to the elimination of the entorhinal input to nucleus accumbens.