Excitatory glutamatergic inputs from limbic regions such as the hippocampus and the
basolateral amygdala (BLA), and dopaminergic inputs from the ventral tegmental area converge
in the nucleus accumbens (NAc). It has been proposed that interactions between these
glutamatergic and dopaminergic pathways play an important role in adaptive behaviors. The
present thesis employed a multidisciplinary approach to study these interactions, with a specific
emphasis on the importance of mesoaccumbens dopamine (DA) transmission, in order to obtain
a better understanding of the neural mechanisms by which the NAc transforms signals from the
temporal lobes into behavior. The experiments of Chapter 2 utilized extracellular single-unit
recordings of individual NAc neurons in combination with electrochemical measures of DA
efflux in the NAc. Recordings from NAc neurons which received input from the hippocampus
but not the BLA revealed that increased efflux of mesoaccumbens DA, evoked by tetanic
stimulation of the fimbria, potentiated hippocampal-evoked neural activity in these cells. These
effects were mediated by both DA and NMDA receptors. Similar recordings from neurons which
received converging input from both the hippocampus and the BLA revealed tetanic stimulation
of the fimbria again potentiated hippocampal evoked spiking activity, while concurrently
suppressing BLA-evoked spiking activity in the same neurons. The suppression of BLA-evoked
spiking activity was activity-dependent, and was mediated by both D, and adenosine A,
receptors. Chapter 3 showed that random foraging on a radial-arm maze, which is dependent on
a neural circuit linking the hippocampus to the NAc, was correlated with an increase in
mesoaccumbens DA extracellular levels, as measured with microdialysis. In Chapter 4,
pharmacological blockade of DA or NMDA receptors in the NAc, or selective disruption of
dopaminergic modulation of ventral subicular inputs to the NAc (using an asymmetrical infusion
procedure) significantly disrupted random foraging. These effects were mediated by the Dl
receptor. In Chapter 5, the present data are integrated with previous research to formulate a
model of ventral striatal function. It is proposed that the NAc mediates behavior through distinct
patterns of activity and inactivity driven by excitatory limbic input projecting to different groups
of neural ensembles. Mesoaccumbens DA transmission plays an essential role in regulating the
synchrony ensemble activity, augmenting activity in one ensemble while suppressing activity in
another. It is argued that the modulatory effects of DA appears to be essential when an organism
must switch from one form of adaptive behavior to another in response to a constantly changing
environment.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU.2429/11410 |
| Date | 05 1900 |
| Creators | Floresco, Stanley Bogdan |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Relation | UBC Retrospective Theses Digitization Project [http://www.library.ubc.ca/archives/retro_theses/] |
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