John Patrick McGann - US grants

DESCRIPTION (Adapted from applicant?s abstract): Behavioral studies have implicated the D2 dopamine receptor in the timing of seconds-range intervals. Separate behavioral investigations have demonstrated that the perirhinal cortex (PR) is important in tasks that require temporal information processing of similar intervals. Recent cellular studies of PR further motivate the idea that PR is involved in temporal aspects of information processing and these ideas have been incorporated into circuit-level computational models. One relevant fact about PR is the large proportion of late-spiking (LS) neurons. These cells delay the onset of their spiking for several seconds relative to the onset of a current clamp step or a train of synaptic inputs. This delay feature is an essential part of the computational model of timing in PR. LS neurons are particularly common in the cortical layers that contain substantial numbers of D2 dopamine receptors. The preceding, taken together, is part of the basis of my interest in exploring the roll of dopamine (DA) physiology in PR, particularly with regard to LS neurons. The overarching idea is that DA alters temporal aspects of information processing in PR by modifying the delay properties of LS neurons through the D2 receptor. The specific hypotheses that I plan to test evaluates the proposition that dopamine can modulate a slowly-inactivating potassium current that is responsible for late-spiking. The results will furnish a conductance mechanism for LS in PR and hopefully elucidate the mechanism by which DA alters this conductance and thereby modulates firing latency in LS neurons. The results should furnish insight into the role of D2 receptors in PR, and as explained inside, are highly relevant to public health.

[unreadable] DESCRIPTION (provided by applicant): Experiments using early sensory deprivation to alter the development of the visual and auditory systems have produced seminal work in those fields. Olfactory deprivation in the neonatal rodent has been shown to evoke dramatic anatomical and neurochemical changes in the olfactory system during development, but little is known about the corresponding functional changes during deprivation and recovery. Dr. Wachowiak and collaborators have demonstrated a transgenic mouse model in which the synaptic terminals of olfactory receptor neurons (ORNs) fluoresce when they release transmitter, permitting the in vivo imaging of ORN synaptic output in the olfactory bulb during odorant presentation. The use of these mice, therefore, provides novel opportunities to investigate the effects of sensory deprivation on the functional development of the olfactory system. The work proposed here will use these mice to study the effects of olfactory deprivation during development on synaptic transmitter release from ORNs and its presynaptic modulation by olfactory bulb circuitry, as well as the recovery from deprivation following the reopening of the naris. This research will provide new insights into the activity-dependent development and regulation of the olfactory system. [unreadable] [unreadable]