There are two long-term objectives of the proposal. First, to understand in neuronal detail how simpler nervous systems are able to generate behaviors and how these nervous systems are able to accomplish simple forms of learning. The second is to understand what happens in cortex during epileptic seizures. In order to better accomplish these scientific goals, we also have the methodological goal of improving optical techniques for monitoring neuron activity. We have been using optical methods to monitor neuron activity in the Aplysia abdominal ganglion during the gill-withdrawal reflex. Our preliminary results suggest that between 250 and 420 neurons in the ganglion are activated by a mechanical stimulus to the siphon. However this estimate comes from a recording that is perhaps 35% complete. We propose experiments to improve the completeness of the recording, experiments to allow preliminary identification of many of these neurons, and analyses to allow us to follow the activity of individual neurons during a series of trials involving habituation and sensitization. We also plan experiments to try to see if the same behavioral plasticity can be achieved with fewer neurons. If this is successful we propose to make a model of the neuron interactions that generate the behavior. We have been able to monitor activity in bicuculline induced inter-ictal epileptiform discharges in rat somatosensory cortex. Our results were surprising in two regards. First, they indicated that the optical measurements and the ball electrode measurements could give very disparate results. Second, they indicated that there were qualitative differences between discharges induced by sensory stimulation and spontaneous discharges.
Our first aim i s to confirm these result. Then we plan a local application of bicuculline to study the spread (or absence of spread) of the epileptic activity away from the treated region. Finally we plan a simultaneous measurement from both the bicuculline treated and the untreated contralateral somatosensory cortex. These experiments are meant to lead toward measurements in more sophisticated models (primates) of the human disease. These experiment may also lead to the use of optical monitoring techniques for determining the location of epileptic foci in surgical patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS008437-20
Application #
3393767
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1977-02-01
Project End
1993-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
20
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Novales Flamarique, IƱigo; Wachowiak, Matt (2015) Functional segregation of retinal ganglion cell projections to the optic tectum of rainbow trout. J Neurophysiol 114:2703-17
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Wu, J Y; Lam, Y W; Falk, C X et al. (1998) Voltage-sensitive dyes for monitoring multineuronal activity in the intact central nervous system. Histochem J 30:169-87
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Wu, J Y; Cohen, L B; Falk, C X (1994) Neuronal activity during different behaviors in Aplysia: a distributed organization? Science 263:820-3
Wu, J Y; Falk, C X; Cohen, L et al. (1993) Optical measurement of action potential activity in invertebrate ganglia. Jpn J Physiol 43 Suppl 1:S21-9
Falk, C X; Wu, J Y; Cohen, L B et al. (1993) Nonuniform expression of habituation in the activity of distinct classes of neurons in the Aplysia abdominal ganglion. J Neurosci 13:4072-81
Loew, L M; Cohen, L B; Dix, J et al. (1992) A naphthyl analog of the aminostyryl pyridinium class of potentiometric membrane dyes shows consistent sensitivity in a variety of tissue, cell, and model membrane preparations. J Membr Biol 130:1-10
Morton, D W; Chiel, H J; Cohen, L B et al. (1991) Optical methods can be utilized to map the location and activity of putative motor neurons and interneurons during rhythmic patterns of activity in the buccal ganglion of Aplysia. Brain Res 564:45-55
London, J A; Cohen, L B; Wu, J Y (1989) Optical recordings of the cortical response to whisker stimulation before and after the addition of an epileptogenic agent. J Neurosci 9:2182-90

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