: The role of hippocampus in memory is well established and the importance of subcortical structures connected to the hippocampus has been known since the pioneering work of Korsakoff and Wernicke. Although certain memory deficits are best described in the frameworks of a diencephalo-hippocanipal syndrome, virtually nothing is known about how these forebrain systems interact with each other and how their interaction is organized by the brainstem so as to account for the robust state dependent changes underlying learning and memory. The central focus of this project is the subcortical regulation of hippocampal function and is guided by the general hypothesis that the role of this regulation is not only to switch the hippocampal EEG between theta and non-theta patterns but also to build dynamic associations between several limbic structures that are synchronized by the theta rhythm. Extrahippocampal theta activity has been recently described in a number of structures under urethane anesthesia but never under natural conditions. The proposed research will test the hypotheses that (1) brainstem/diencephalic systems, in addition to switching between theta and non-theta take part in behaviorally-related fine tuning of hippocampal activity during natural theta states; (2) theta rhythmic activity plays a role in neuronal cooperation between different limbic structures and brainstem structures exhibiting theta rhythmic activity specifically regulate this traffic; (3) theta rhythmic activity generated in the septum and the mammillaiy complex exerts feedback regulatory influence on brainstem nuclei involved in brain state regulation. Phasic and rhythmic synchronization of neuronal activity is critical to the concerted action of spatially separated structures in the brain. Theta synchrony provides an excellent model to study such cooperation and the way in which it differs in specific behavioral states. Our experiments will take advantage of waking exploration and sleep as a natural experiment trying to inform us about the components of the memory building process. The timeliness of this work is underlined by the recent upsurge of interest and data linking sleep, hippocampal activity and successive phases of information processing in non-REM and REM sleep.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
7R01MH062525-03
Application #
6607970
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (01))
Project Start
2001-09-06
Project End
2006-06-30
Budget Start
2002-07-03
Budget End
2003-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$254,848
Indirect Cost
Name
Harvard University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Sorman, Elin; Wang, Dannie; Hajos, Mihaly et al. (2011) Control of hippocampal theta rhythm by serotonin: role of 5-HT2c receptors. Neuropharmacology 61:489-94
Lanre-Amos, Tope; Kocsis, Bernat (2010) Hippocampal oscillations in the rodent model of schizophrenia induced by amygdala GABA receptor blockade. Front Psychiatry 1:132
Hajos, Mihaly; Hoffmann, William E; Kocsis, Bernat (2008) Activation of cannabinoid-1 receptors disrupts sensory gating and neuronal oscillation: relevance to schizophrenia. Biol Psychiatry 63:1075-83
Hajos, M; Siok, C J; Hoffmann, W E et al. (2008) Modulation of hippocampal theta oscillation by histamine H3 receptors. J Pharmacol Exp Ther 324:391-8
Dahan, Lionel; Astier, Bernadette; Vautrelle, Nicolas et al. (2007) Prominent burst firing of dopaminergic neurons in the ventral tegmental area during paradoxical sleep. Neuropsychopharmacology 32:1232-41
Hajos, Mihaly; Allers, Kelly A; Jennings, Katie et al. (2007) Neurochemical identification of stereotypic burst-firing neurons in the rat dorsal raphe nucleus using juxtacellular labelling methods. Eur J Neurosci 25:119-26
Kocsis, Bernat (2006) The effect of descending theta rhythmic input from the septohippocampal system on firing in the supramammillary nucleus. Brain Res 1086:92-7
Kocsis, Bernat; Kaminski, Maciej (2006) Dynamic changes in the direction of the theta rhythmic drive between supramammillary nucleus and the septohippocampal system. Hippocampus 16:531-40
Li, Shaomin; Varga, Viktor; Sik, Attila et al. (2005) GABAergic control of the ascending input from the median raphe nucleus to the limbic system. J Neurophysiol 94:2561-74
Kocsis, Bernat; Li, Shaomin (2004) In vivo contribution of h-channels in the septal pacemaker to theta rhythm generation. Eur J Neurosci 20:2149-58

Showing the most recent 10 out of 14 publications