No description available.

No description available.

No description available.

This study investigated the distribution of CB1 and VR1 receptors in rat cultured hippocampal and sensory cells and in the myenteric plexus of various rodents. CB1 and VR1 receptor-immunoreactivity was observed in a subset of neurones and their processes. Primary sensory neurones expressed CB1 receptors on their soma and fibres. The vast majority of CB1 receptor-expressing hippocampal neurones were GABAergic but appeared to be VR1 receptor-immunonegative. Cannabinoid agonists inhibited the expression of cell surface CB1 receptors in a concentration-dependent, stereoselective manner. This inhibition of cell surface labelling was maximal at 16 h, did not require the activation of Gi/o-proteins and was abolished in the presence of SR141716A, a selective CB1 receptor antagonist. A new primary antibody pre-labelling protocol demonstrated that this inhibition reflects agonist-induced internalisation and suggests that internalised CB1 receptors are translocated from axons towards somatodentritic regions. In F-11 cells, shown here to naturally express CB1 receptors on their somatic membrane, cannabinoid-induced internalisation occurred within a relatively short period (30 min). In the guinea-pig and rat myenteric plexus, virtually all CB1 and VR1 receptor- immunopositive cells were cholinergic. Subpopulations of calbindin-, calretinin- and neurofilament protein-immunopositive neurones co-expressed either receptor type. The localisation of VR1 receptors in calcitonin gene-related peptide-positive fibres and the expression of CB1 receptors in their somata implies a role for VR1 receptors in neuropeptide release and identified CB1 receptor-containing secretory neurones. There was also a close association between CB1 and VR1 receptor-immunoreactivity and fibres labelled for synaptic protein, suggesting roles for these receptors in the modulation of neurotransmitter release. These results are consistent with the inhibition by cannabinoids of neurotransmitter release and gastrointestinal transit and peristalsis. Internalisation of CB1 receptors may be a mechanism by which neurones control sensitivity to endocannabinoids and regulate the development of tolerance to cannabinoid drugs. The co-localisation studies in the gut identified intrinsic sensory, interneuronal and motor neurones expressing CB1 and VR1 receptors.

No description available.

No description available.

The adult mammalian brain harbours at least two germinal - or neurogenic - niches in which new neurons are born throughout life. These neurogenic niches comprise the subependymal zone which lines the ventricular system, and the subgranular zone in the hippocampal dentate gyrus. Post-natal hippocampal neurogenesis was in fact first identified experimentally in the 1960s. However perhaps due partly to aforementioned institutionalised belief and partly to a lack of accessible experimental tools, the phenomenon of hippocampal neurogenesis was widely recognised by the scientific community only shortly before the millennium. Consequent study has established that adult hippocampal neurogenesis has been conserved through millions of years of evolution in nearly every mammalian species studied to date. Importantly, post-mortem studies and radioisotope carbon dating techniques suggest that it also occurs in humans. A great deal of this research has focused on understanding the inner workings of the cells that undergo the transformation to become new adult-born neurons. By contrast, relatively little is known about the potential regulatory role of the surrounding extracellular microenvironment. This might be useful to know in light of much evidence that the extracellular matrix is a key regulator of developmental neurogenesis. This thesis describes my study of whether extracellular matrix regulates hippocampal neurogenesis.

<p> Relationships between dorsal hippocampal EEG and behavior were studied in the rat. Walking etc, and lever pressing were associated with significantly more hippocampal RSA than operant licking, normal drinking, polydipsic drinking, grooming, saliva spreading and holding still. The results suggested that hippocampal EEG is related to the form of response, rather than to perceptual or sensory processes or to central integrative processes. Furthermore, the results suggested that hippocampal EEG is not related to the operant role of response or to relative intensities of response. </p> / Thesis / Doctor of Philosophy (PhD)

Emerging evidence suggests that hippocampal memory processing is modulated by midbrain regions under conditions of reward, resulting in enhanced encoding of episodic information—long-term memory for events. Current theories further suggest that hippocampal subregions may have distinct roles in episodic memory formation, and may be differentially influenced by dopaminergic midbrain inputs. Using high-resolution functional magnetic resonance imaging (fMRI), the present study investigated hippocampal subregional function as well as activation in surrounding medial temporal lobe (MTL) cortex, midbrain, and nucleus accumbens during associative encoding and cued recall under varying conditions of reward. A high-value or low-value monetary cue preceded a pair of objects indicating potential reward for successful retrieval of the association. At test, participants performed cued recall followed by match (correct association) or mismatch (incorrect association) probe decisions and received feedback on their performance. Behaviorally, cued recall performance was superior for pairs preceded by high reward cues at encoding relative to pairs preceded by low reward cues. FMRI analysis revealed regions within hippocampus, parahippocampal cortex, nucleus accumbens, and midbrain showing subsequent memory effects (greater encoding activation for remembered, compared to forgotten associations) and reward effects (greater activation for high-value, compared to low-value associations) during stimulus encoding. Within several of these regions, individual differences in reward-related encoding activation were correlated with the degree of the behavioral reward effect (better memory for high-value compared to low-value object pairs). At retrieval, regions in midbrain and subiculum predicted successful associative recall, and regions within hippocampus, parahippocampal cortex, nucleus accumbens, and midbrain showed reward effects in the absence of explicit reward cues. Within several MTL regions, activation was greater for match than mismatch probes. These findings are consistent with theories suggesting that reward-based motivation influences memory formation through interactions between dopaminergic midbrain and hippocampus. / text

No description available.