The hippocampal Theta rhythm of the rat is an ideal model system for studying the generation of rhythmic slow waves in the brain. The mechanisms of naturally occurring slow waves are poorly understood at the present time, yet this information is crucial for understanding the generation of pathological slow waves. Knowledge of the mechanisms of theta rhythm may also suggest hypotheses about its function. This proposed project aims to discover which components of the intrahippocampal circuitry are involved in the generation of the theta rhythm. There are at least two types of theta rhythm. One of these occurs during motionless behaviors and urethane anesthesia and is abolished by atropine. This last fact is taken as evidence that muscarinic cholinergic receptors are involved in its generation. The second type of theta rhythm occurs during walking and postural adjustments, but not during relatively """"""""automatic"""""""" motor behaviors like chewing. Several studies from this laboratory have shown differences in the mechanisms of the two. The theta rhythm induced by urethane is easier to study, but the theta rhythm induced by walking is more interesting because it is present at a time when the hippocampus may be very active in guiding the rat's behavior. Recordings form hippocampal pyramidal cells in freely-moving rats have shown that they first lost rapidly when the rat is in a particular part of its environment, as if they were extracting """"""""place"""""""" information from multmodal sensory cues. The walking-induced theta rhythm occurs naturally as the rat moves from place to place and it represents oscillations of the membrane potentials of these same pyramidal cells, so it may be involved in this extraction process. This project proposes studies designed to contribute to our understanding of these two theta rhythms by: 1) determining the sources of extracellular current in order to locate active synaptic sites and b) making intracellular recordings and input immpedance measurements from all hippocampal cell types to determine the nature of the synaptic potentials related to theta rhythm and to provide additional information on their locations. These data when put together with existing data relating the phase of the theta rhythm with a) the extracellularly recorded firing of hippocampal neurons and b) the excitability of projection cells will allow strong conclusions to be made about the sequence of activity during a cycle of theta rhythm and the circuitry underlying its generation.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology A Study Section (NEUA)
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Suny Downstate Medical Center
Schools of Medicine
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Brazhnik, Elena; Borgnis, Ramie; Muller, Robert U et al. (2004) The effects on place cells of local scopolamine dialysis are mimicked by a mixture of two specific muscarinic antagonists. J Neurosci 24:9313-23
Brazhnik, E S; Muller, R U; Fox, S E (2003) Muscarinic blockade slows and degrades the location-specific firing of hippocampal pyramidal cells. J Neurosci 23:611-21
Brazhnik, E S; Fox, S E (1999) Action potentials and relations to the theta rhythm of medial septal neurons in vivo. Exp Brain Res 127:244-58
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Brazhnik, E S; Fox, S E (1997) Intracellular recordings from medial septal neurons during hippocampal theta rhythm. Exp Brain Res 114:442-53
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Ludvig, N; Altura, B T; Fox, S E et al. (1995) The suppressant effect of ethanol, delivered via intrahippocampal microdialysis, on the firing of local pyramidal cells in freely behaving rats. Alcohol 12:417-21
Ludvig, N; Potter, P E; Fox, S E (1994) Simultaneous single-cell recording and microdialysis within the same brain site in freely behaving rats: a novel neurobiological method. J Neurosci Methods 55:31-40
Brankack, J; Stewart, M; Fox, S E (1993) Current source density analysis of the hippocampal theta rhythm: associated sustained potentials and candidate synaptic generators. Brain Res 615:310-27
Stewart, M; Luo, Y; Fox, S E (1992) Effects of atropine on hippocampal theta cells and complex-spike cells. Brain Res 591:122-8

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