| Anton Khabbaz |
 My project aims to elucidate the cellular and network mechanisms
underlying a form of short-term memory at work in the head
direction (HD) system of a behaving transgenic mouse. A central question in neuroscience over the last century has been how the brain maintains memories. In primates it was first demonstrated that sustained, elevated rates of action potential firing accompany one form of memory called short-term or working memory. This firing persists while the memory is held and stops once the relevant motor output is made. The mechanisms used to maintain this persistent neural activity, has been studied extensively in the Tank Lab (http://genomics.princeton.edu/tank/Index.html) experimentally and theoretically using a model system, the oculomotor system of the goldfish. The head direction system, a neural circuit that encodes and stores an animal's sense of direction, is another promising model system for short-term memories (Figure 1). Head Direction (HD) cells selectively fire action potentials at a sustained, elevated rate when the animal points its head in a particular direction in the horizontal plane relative to landmarks in its environment as in Figure 1. HD cells fire when the head is oriented in this preferred direction; independently of body orientation and the animal's location. Because HD activity remains when sensory cues (such as all visual landmarks) are eliminated, this activity also has the characteristic of a short-term memory. HD cells have been studied in rat largely by studying a single neuron at a time. My goal is to simultaneously measure multiple, well isolated
HD neurons in a transgenic mouse. I now have developed an
ultra-light microelectrode array that locates 5 individually
adjustable electrodes within a single HD nucleus which is less
than 250 microns in diameter, 3 mm deep in the brain (Figure 2).
Furthermore a complex surgical technique now allows us to
consistently implant the array to reach the center of this deep
difficult to reach nucleus. This work has resulted in the only
measurement of mouse HD cells to date (Figure 3). The
experimental arena with an ultra-light pre-amplifier and cable,
and infrared LEDs This research may have broad significance for neuroscience for several reasons. Firstly, this system allows the study of a form of short-term memory with multiple probes invasively in a system that can be manipulated genetically. The HD system requires no training (unlike the primate experiments), and the location of the critical nuclei are well established. Secondly, the electrode method developed here allows measurement of multiple single neurons in any small nucleus of a mouse, and should find applicability by other laboratories that want to study more than one neuron simultaneously in the same circuit, a topic of general interest in systems neuroscience. Thirdly, the continuous attractor model studied for HD cells has also been proposed for a variety of other systems, so the cellular and network mechanisms elucidated here could very well generalize to other examples of persistent firing and short-term memory. |
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| Last Updated ( Tuesday, 13 March 2007 ) |
records HD cells and the head angle while allowing
the mouse to run, jump and forage for food freely. By performing
HD experiments in transgenic mice, it is possible to manipulate
candidate genes to alter circuit properties much more precisely
than by other means. The N-methyl-D-aspartate (NMDA) receptor has
the longest gating time of any receptor and has been hypothesized
to play a key role in the HD circuit. Appropriate transgenic mice
for the HD system are being developed in the Tsien Lab (