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The processing of sensory signals is an important, yet complex task in which a system must extract behaviorally relevant stimulus patterns from a vast array of sensory cues. When a neuron within a major sensory area is presented with a stimulus, one of the important characteristics used to distinguish between types of input is frequency. Often sensory neurons are tuned to narrow stimulus frequency ranges and are thus charged with the processing of subtypes of sensory signals. The weakly electric fish Apteronotus lepthorhynchus senses it's environment through modulations of a self-generated electric field. Two main types of sensory signals can be distinguished based on their frequency patterns. Prey stimuli cause low frequency perturbations of the electric field, while communication signals often result in high frequency signals. Pyramidal neurons in the electrosensory lateral line lobe (ELL) encode the low frequency signals with bursts, while the high frequency signals are relayed with single spikes. This thesis describes how a pyramidal neuron's response patterns can be tuned to specific frequencies by the expression of distinct classes of potassium channels. / I have cloned 3 small conductance (SK) calcium activated potassium channels from cDNA libraries created from the brain of Apteronotus. I have subsequently localized the AptSK channels throughout the brain using both in situ hybridization (AptSK1, 2 & 3) and immunohistochemical (AptSK1 & 2) techniques. The 3 channels showed distinct expression patterns, with the AptSK1 & 2 channels showing a partially overlapping expression pattern, while AptSK3 appears to be expressed in unique areas of the brain. In the ELL AptSK1 & 2 show a partially overlapping expression pattern, appearing in similar pyramidal neurons. However, their distribution within individual cell is unique, with AptSK1 showing a dendritic localization, while AptSK2 is primarily somatic. We have demonstrated that the unique expression pattern of the somatic AptSK2 channel in the ELL coincides with the functional SK currents evaluated through in vitro electrophysiology. Further we have shown that neurons that encode low frequencies do not possess functional SK channels. It thus appears that the presence of the AptSK2 channel subtype can predispose a neuron to respond to specific types of sensory signals. / In an attempt to evaluate if second messengers could modify the AptSK control of frequency tuning I investigated the consequences of muscarinic acetylcholine receptor (mAChR) activation on a pyramidal neurons response patterns. While it had been shown in vivo that mAChR activation increased a pyramidal neuron's response to low frequencies, I have found that this was not due to a decrease in AptSK current, but rather appears to be the result of a down-regulation of an A-type potassium channel. / Taken together the studies that comprise this thesis show how the selective expression of a single potassium channel subtype can control a sensory neurons response to specific environmental cues. The secondary modulation of the A-type current highlights the potential for a second messenger to control a neuron's sensory response through the down-regulation of constitutively expressed potassium current.

Members of voltage-gated potassium channel subfamily 3 (Kv3) have been extensively demonstrated to play a significant role in facilitating function of "fast-firing" neurons in the central nervous system. Kv3.1 and Kv3.3 channels, members of Kv3 channel subfamily, have different distribution profiles on the regional level of brain and on the subcellular level of neurons in mammals and in weakly electric fish, according to mRNA hybridizations in situ and immunohistochemical analysis. In mammals, Kv3.1 channels are expressed in soma, axon and proximal dendrites as well as presynaptic membrane of "fast-firing" neurons. In weakly electric fish (Apteronotus), Kv3.1 channels are distributed in the soma, in the basilar dendrites and in the proximal apical dendrites of pyramidal neurons; on the other hand, Kv3.3 channels are expressed in a larger region: soma, basilar dendrites and entire apical dendrites of these cells. Mechanisms underlying differential subcellular distribution of Kv3.1 and Kv3.3 channels in the apical dendritic compartment of pyramidal neurons are unknown. In order to identify peptide sequences responsible for the differential subcellular localization, I have used Semliki Forest virus as a modified viral expression system (PDE) in vivo to study dendritic targeting mechanisms in the pyramidal neurons of electrosensory lateral line lobe (ELL), where the primary processing for afferent input occurs in the apteronotid electrosensory system.

Partial cDNAs for each of the four known N-methyl-D-aspartate (NMDA) receptor 2 (NMDAR2A-D) subunits have been cloned from the brain of A. leptorhynchus and are found to display a high degree of sequence homology (83--78% amino acid identity) to their mammalian homologues. In situ hybridization experiments reveal that each transcript has a distinct expression pattern in the apteronotid central nervous system (CNS) and is present in a "mosaic" distribution within important cell types of the electrosensory lateral line lobe (ELL). Apt. NMDAR2A transcript is expressed in forebrain regions as well as throughout the pyramidal cell layer (PCL) and granule cell layer (GCL) of the ELL. Apt. NMDAR2B mRNA is enriched in mid- and forebrain structures as well as the PCL and GCL of the ELL. Apt. NMDAR2C transcript is largely restricted to cerebellar regions but is also found in the PCL and GCL of the ELL's medial, centromedial, and centrolateral segments. Apt. NMDAR2D mRNA is expressed in sites of cell proliferation and in a segmental gradient within granule cells of the ELL.

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