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Title: An investigation of the neural basis of associative recognition memory in the rat
Author: Savalli, Giorgia
ISNI:       0000 0004 2722 5656
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2012
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Object-in-place (OIP) memory is a form of associative recognition memory which relies on the formation of an association between an object and the place in which such object was encountered. Existing evidence shows that OIP memory depends upon a circuit of neural regions which include the medial prefrontal cortex (mPFC), perirhinal cortex (PRH) and hippocampus (HPC). The aim of this thesis was to characterise further the cellular mechanisms which underlie OIP associative memory in the rat. Several lines of research have shown that mPFC, PRH and HPC receive a substantial dopaminergic projection and that in these areas dopamine plays a critical role in modulating plasticity and memory processes. In the first part of this thesis the role of dopamine neurotransmission within mPFC, PRH and HPC for OIP memory was investigated. Guide cannulae were implanted in the regions of interest to allow local infusion of the selective dopamine D1 receptor antagonist SCH23390 and OIP memory was tested using a spontaneous OlP memory task. Oopaminergic neurotransmission through D1 receptors was found to be required in mPFC for acquisition, but not for consolidation or retrieval, of both short-term and long-term OlP memory. In contrast direct infusion of SCH23390 into PRH or HPC produced no impairment in memory. Further, a possible role of dopamine through D2 receptors was excluded, as intra-mPFC infusion of the D2 receptor antagonist eticlopride did not cause any impairment in the task. These results demonstrated that dopaminergic neurotransmission via 01 receptors was selectively involved in the acquisition of OIP memory in the mPFC. The next series of experiments investigated the synaptic plasticity mechanism underlying long-term (24 h) OIP memory within the mPFC. Local blockade of PKMzeta, a protein critical for LTP, through infusion of the selective inhibitor ZIP, impaired OIP memory performance either when infused prior the sample or 5 h before the test. an the contrary, infusion of the synthetic peptide GluR2-3Y, a molecule critical for LTO, either before the sample phase or 5 h before the test, did not show any memory impairment. These findings suggested that an LTP-like, rather than an LTO-like, mechanism occurs both during the encoding and the maintenance of OIP memory. The final series of experiments presented in this thesis aimed to investigate whether other brain regions, beyond mPFC, PRH or HPC, were involved in OlP associative recognition memory. Neuronal activity was measured through the differential expression of the immediate early genes c-fos and zif268, following presentation of novel or familiar arrangements of visual stimuli. However here were no significant differences in levels of neuronal activation following the presentation of novel and familiar stimuli in any of the areas analysed, a finding which may relate to procedural issues in the presentation of the visual stimuli.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available