L-type calcium channels modulate firing patterns of ventral tegmental area neurons

Pittman, Andrea Nicole (2012) L-type calcium channels modulate firing patterns of ventral tegmental area neurons. Masters thesis, Memorial University of Newfoundland.

[English] PDF (Migrated (PDF/A Conversion) from original format: (application/pdf)) - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (33MB) [English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. (Original Version)

Abstract

Neurons originating in the ventral tegmental area (VTA) have been implicated in disease states such as drug addiction and schizophrenia. It is believed excessive dopamine transmission (via dopaminergic neuron excitation) underlies both disease states. As dopamine is released because of action potential firing, more intense spiking will result in more neurotransmitter being released. Therefore, understanding the mechanisms modulating firing patterns may lead to a better understanding of such diseases. -- This thesis seeks to compare the basic electrophysiological properties of dopaminergic (DAergic) and GABAergic neurons within the VTA, as well as to identify how L-type calcium channels (LTCC) modulate firing patterns of both cell populations. Using a mouse model with green fluorescent protein labeled DAergic neurons, combined with patch clamp recordings, I find two commonly used fingerprinting criteria, Ih current and dopamine autoinhibition, are specific to DAergic neurons. As well, using an LTCC transgenic mouse model and various LTCC modulators, I show LTCC activation modulates burst firing similarly in DAergic and non-DAergic neurons of the VTA. More specifically, the Cav1.3 subtype is responsible for this LTCC induced bursting. -- Understanding the intrinsic modulators of firing pattern regulation in both DAergic and non-DAergic neurons of the VTA can provide a better understanding of disease states associated with dopamine transmission dysregulation, potentially leading to a target for future treatment options.

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