Psychology ETDs

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The hippocampus is essential for long-term memory storage and consolidation. The dentate gyrus acts as a gateway into the hippocampal formation, specifically with reference to medial and lateral perforant path projections from the entorhinal cortex. The dentate gyrus and the hippocampus contain a high density of cannabinoid receptors and may be a key location in which cannabinoids exert influence to disrupt memory. Administration of a cannabinoid agonist often leads to short-term and long-term memory deficits in a variety of tasks. Cannabinoids can impair memory acquisition, task performance, along with memory consolidation and retrieval mechanisms. Endogenous cannabinoids are retrograde messengers involved in the rapid modulation of synaptic transmission. In the following study the effects of a potent cannabinoid agonist, WIN 55,212-2, on rodent learning and memory in the dentate gyrus were examined using a combination of morphological, behavioral, electrophysiological, and gene targeting approaches. The current study found that the cannabinoid agonist, WIN 55,212-2, altered granule cell spine density in the dendritic targets of the associational-commissural afferents and medial perforant path projections, but not lateral perforant path. Although intraperitoneal injections of WIN 55,212-2 resulted in a 24-hour consolidation deficit mediated by CB1 receptors, direct infusion of WIN 55,212-2 into the dentate gyrus did not influence 24-hour memory consolidation or alter immediate early gene expression in the dentate gyrus or parietal cortex. When examining in vivo electrophysiology, the cannabinoid agonist altered perforant path to dentate gyrus responses. WIN 55,212-2 blunted the magnitude of baseline population spike amplitude, without changing baseline fEPSP response. Furthermore, WIN 55,212-2 altered fEPSP paired pulse facilitation indicating decreased glutamate release and impaired GABAergic inhibition. Conversely, following high frequency stimulation, WIN 55,212-2 increased fEPSP fractional change. And lastly, WIN 55,212-2 elevated expression of the immediate early gene Arc in the high frequency stimulated dentate gyrus. These findings indicate cannabinoid modulation throughout the dentate gyrus and hippocampus is necessary for memory consolidation processes. When taken together, these results suggest cannabinoids alter normal learning and memory processes in the dentate gyrus by selectively altering medial perforant path projections, changing GABAergic feedforward inhibition, reducing glutamate release, and increasing expression of the immediate early gene Arc.

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First Committee Member (Chair)

Caldwell, Kevin

Second Committee Member

Yeo, Ron

Third Committee Member

Weisend, Michael




Cannabinoid, Hippocampus, Dentate gyrus, Synaptic plasticity, Morris water task, Golgi-Cox, Long-term potentiation, Paired-pulse facilitation

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