Identification of ion channels and their roles in neurons of the piriform cortex

Date

2023

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Aung, Khaing Phyu

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Abstract

The piriform cortex (PC), a trilaminar paleocortex, is the first cortical destination of olfactory information. Compared to the six-layered neocortex, the anatomically simpler PC is an ideal model system for understanding cortical sensory processing. As in other brain areas, the anterior PC (aPC) contains glutamatergic (excitatory) and GABAergic (inhibitory) neurons. Based on their characteristics, such as morphology, firing properties and expression of neuronal markers, different subtypes of excitatory and inhibitory neurons have been identified. Action potential (AP) firing properties are fundamental to the way in which neurons encode and transmit information. Given the diversity of AP firing properties in different neuronal subtypes in aPC, it is important to study the causes of this diversity in order to understand the complex functions of this neuronal network. In contrast to well-studied brain areas like the hippocampus, in the aPC only a few properties of APs have been studied, mainly in excitatory neurons. Very little is known about interneurons, even though they are found to be essential for physiological function of sensory circuits in other cortical regions. In this thesis, I focused on identifying the ion channels responsible for the distinctive firing patterns of some of the neurons in aPC. First, I focused on a class of unusual inhibitory interneuron, the horizontal (HZ) cell. By using current clamp recordings in combination with specific channel blockers, the roles of calcium-activated potassium (KCa) channels in AP firing were identified in HZ cells. One type of KCa channel, the large-conductance (BKCa) channel, was found to be partly responsible for AP repolarization and the fast afterhyperpolarization (fAHP), but had no effect on the firing pattern in response to a long depolarizing current step. On the other hand, another type of KCa channel, the small-conductance (SKCa) channel was found to be solely responsible for the medium afterhyperpolarization (mAHP) and its blockade had a strong effect on the firing pattern. Next, using both voltage-clamp and current-clamp approaches, the subtypes of CaV channels present in HZ cells were identified, together with their roles in firing properties. Interestingly, it was found that HZ cells did not express L-type CaV channels, while T-, N-, P/Q-, and R-type CaV channels were all present and responsible for similar percentages of total Ca2+ entry in the perisomatic region of these cells. . I next used similar techniques to study two major classes of excitatory neurons in the aPC, semilunar (SL) and superficial pyramidal (SP) cells. It was found that four different subtypes of CaV channel were mainly responsible for Ca2+ entry in the perisomatic region of SL cells: L-, T-, P/Q-, and R-subtypes while in SP cells there were three main subtypes: L-, T- and R-subtypes. In SP cells, Ca2+ entry through L type CaV channels acted as the main activator of BKCa channels. Regarding SKCa channels, the average number of APs in 1 s was significantly increased when ~68% of total Ca2+ entry was blocked in SL cells, whereas in SP cells it only changed significantly when all CaV channel subtypes were blocked in the perisomatic region. Nevertheless, in SP cells, the instantaneous firing pattern was significantly changed when more than one CaV channel subtype was blocked in the perisomatic region. These findings reveal surprising differences among these cell types, including varying contributions by CaV channel subtypes to Ca2+ entry, different Ca2+ sources for BKCa and SKCa channel activation, and different effects of these channel subtypes on AP firing patterns. Further studies on other ion channels and other subtypes of neurons in the aPC will likely further clarify the operation of this sensory circuit.

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Thesis (PhD)

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DOI

10.25911/6TPB-2R69

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