Text

theses

ETD doctoral

The term basal forebrain (BF) refers to a collection of nuclei found in the ventromedial aspects of the mammalian forebrain. The cholinergic corticopetal neurons in these nuclei received particular attention due to the intricate involvement of acetylcholine in cardinal cognitive functions. These neurons are referred to as the basal forebrain cholinergic (BFc) neurons and constitute the BFc system. This thesis asks three questions regarding the BFc system. The first question (Aim 1) pertains to the electrophysiological properties of its constituent neurons. Second question (Aim 2) deals with their interactions. The final question (Aim 3) is aimed at answering how these neurons modulate cellular properties in target neurons, considering the regular-spiking (RS) basolateral amygdala (BLA) neurons as a model system. To answer these questions, patch-clamp recordings in acute brain slices obtained from transgenic mice were done. The cholinergic effects on BFc neurons themselves and RS-BLA neurons were studied via optogenetically stimulating BFc neurons. Aim 1 revealed that BFc neurons can be differentiated into two electrophysiologically identifiable subtypes: early and late firing neurons. Early firing neurons (70%) are more excitable, show prominent spike frequency adaptation and are more susceptible to depolarization blockade, a phenomenon characterized by complete silencing of the neuron following an initial discharge of action potentials. Late firing neurons (30%), albeit being less excitable, could maintain a tonic discharge at low frequencies. In Aim 2, the inhibitory nature of BFc interactions were revealed using different approaches of slice electrophysiology that include the application of cholinergic agonists/antagonists, paired whole-cell recordings, and optogenetic activation of a subset of BFc neurons while recording the postsynaptic responses in others. The mechanisms and potential functional implications of these inhibitory actions are discussed in detail later. Experiments in Aim 3 were concerned with the effects of endogeneously released acetylcholine on RS-BLA neurons. The results reveal that cholinergic action depends on the recent history of RS-BLA neurons: It is excitatory following high frequency prior spiking while muscarinic inhibition dominates during lower firing frequencies. These results might point out to a thresholding function of acetylcholine in vivo.

ETD_4483

http://hdl.rutgers.edu/1782.1/rucore10002600001.ETD.000067624

doi:10.7282/T3D79945

Ph.D.

Includes bibliographical references

Includes vita

by Çağri Temuçin Ünal

The author owns the copyright to this work.