A GENETIC APPROACH TO C. ELEGANS CHOLINERGIC SIGNALING

Genes that are involved in localization or modulation of neurotransmitter receptors are difficult to identify. We generated a C. elegans strain expressing a mutated, hyperactivitied acetylcholine receptor. These animals display a dramatic movement phenotype, as well as mislocalization of a related receptor. Our genetic screen for suppressors of the movement phenotype isolated 15 suppressors, many of which would not have been isolated using traditional methods. We believe that this strategy will find novel factors that play important roles in cholinergic signaling

Theta oscillations, timing and cholinergic modulation in the rodent hippocampal circuit

The medial temporal lobe (MTL) is crucial for episodic and spatial memory, and shows rhythmicity in the local field potential and neuronal spiking. Gamma oscillations (>40Hz) are mediatepd by local circuitry and interact with slower theta oscillations (6-10 Hz). Both oscillation frequencies are modulated by cholinergic input from the medial septum. Entorhinal grid cells fire when an animal visits particular locations in the environment arranged on the corners of tightly packed, equilateral triangles. Grid cells show phase precession, in which neurons fire at progressively earlier phases relative to theta oscillation as animals move through firing fields. This work focuses on the temporal organization of spiking and network rhythms, and their modulation by septal inputs, which are thought to be involved in MTL function. First, I recorded grid cells as rats explored open spaces and examined precession, previously only characterized on linear tracks, and compared it to predictions from models. I identified precession, including in conjunctive head-direction-by-grid cells and on passes that clipped the edge of the firing field. Secondly, I studied problems of measuring single neuron theta rhythmicity and developed an improved approach. Using the novel approach, I identified diverse modulation of rat medial entorhinal neurons’ rhythmic frequencies by running speed, independent from the modulation of firing rate by speed. Under pharmacological inactivation of the septum, rhythmic tuning was disrupted while rate tuning was enhanced. The approach also showed that available data is insufficient to prove that bat grid cells are arrhythmic due to low firing rates. In the final project, I optogenetically silenced cholinergic septal cells while recording from hippocampal area CA1. I identified changes in theta rhythmic currents and in theta-gamma coupling. This silencing disrupted performance when applied during the encoding phase of a delayed match to position task. These data support hypothetical roles of these rhythms in encoding and retrieval and suggest possible mechanisms for their modulation. Together, evidence from these projects suggests a role for theta in the function of spatial and episodic memory. These oscillations have important implications for communication and computation, and they can provide a substrate for efficient brain function

EduVentures WebExpedition

This project, sponsored by EduVentures and the National Museum of Namibia, sought to increase Namibian secondary students\u27 awareness of biodiversity by creating and deploying a computer game called WebExpedition. We received input from teachers and students to optimize the game\u27s usefulness and effectiveness, and performed trial runs with Namibian students. The game teaches students about scientific classification of organisms, and allows students to connect animals and plants to their habitats in Namibia