The activity of neurons in the prefrontal cortex (PFC) may underlie working
memory processes in the brain. Both the performance of working memory tasks
and the activity of PFC neurons are modulated by dopamine. The goal of the
present thesis was to gain insight into the neural basis of working memory by
studying the PFC, and the DA system in the PFC, from both a behavioral and
cellular perspective.
The functional contribution of the PFC to working memory processes in the rat
was assessed in Chapter 2 of the present thesis using memory-based foraging
tasks on an 8-arm radial maze. The results of these studies indicated that
lidocaine-induced inactivations of the PFC selectively disrupted the ability to use
mnemonic information to guide foraging, but not the ability to acquire or retain
such information. The ability to use mnemonic information to guide foraging was
also disrupted by microinjection of a D1 but not D2 receptor antagonist into the
PFC.
Chapters 3-5 investigated how PFC neurons process synaptic inputs to their
dendrites to produce spike output. The intrinsic membrane properties and
synaptic responses at the soma and dendrites of deep layer PFC pyramidal
neurons were recorded using sharp intracellular or whole-cell patch-clamp
techniques in a brain-slice preparation. Different passive and active membrane
properties of the soma and dendrites of PFC neurons were observed. The distal
dendrites of PFC neurons responded most effectively to strong, highly coincident synaptic inputs. Ca²⁺currents near the soma both amplified the effects of these
inputs and modulated the spike output pattern. Spike output at the soma was
also controlled by the interplay of slowly-inactivating Na⁺ and K⁺ currents.
Chapter 6 investigated the modulation of PFC neurons by DA. DA or a D1 but not
D2 receptor agonist increased the evoked firing of PFC neurons via a D1-
mediated modulation of slowly-inactivating Na⁺ and K⁺ currents. Concurrently, D1
receptor activation reduced burst firing in PFC neurons, due to a attenuation of
Ca²⁺ currents. D1 receptor activation also increased both GABA[sub A] IPSPs and
NMDA EPSPs.
The final chapter of this thesis integrated these data into a cellular model of PFC
function and its modulation by DA. It is proposed that DA may tune PFC neurons
such that they respond selectively to strong synchronized inputs from other
cortical areas. In the presence of DA, working memory processes mediated by
the PFC may be influenced selectively by stimuli of behavioral significance.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU.2429/8557 |
| Date | 05 1900 |
| Creators | Seamans, Jeremy Keith |
| 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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