In previous studies, we demonstrated that the nucleus pontis oralis (RPO) and the median raphe nucleus (MR) are directly involved in the synchronization (theta) and desynchronization of the hippocampal EEG, respectively, and further that the supramammilliary nucleus (SUM) is a critical relay between the brainstem and septum hippocampus in the control of the theta rhythm. The proposed studies are divided into two parts; those done with and without collaborators. Non-collaborative studies and the primary aims of the non-collaborative studies are: (1) to examine whether the SUM exerts an indirect (through the septum) and/or direct influence on the hippocampus in the generation of theta by analyzing the effects on the hippocampal EEG of injections of ibotenic acid or the cholinergic neurotoxin, 192 IgG saporin into the medial septum diagonal band; and (2) to characterize the role of several brainstem/diencephalic nuclei putatively involved in the control of hippocampal synchronization (pedunculopontine tegmental nucleus, nucleus reuniens, mammillary body, posterior nucleus of hypothalamus and SUM) and desynchronization (lateral habenula and MR) by examining the connections of these nuclei, their response to pharmacological agents and their neuronal discharge properties in anesthetized and freely moving rats. Collaborative Studies: These studies will be done in collaboration with Dr. Angel Alonso (electrophysiology in slices), Dr. Csaba Leranth (electron microscopy) and Dr. Matthew L. Shapiro (behavior). The primary aims of the collaborative studies are: 1) to examine the electrophysiological properties and response to various transmitter agents of SUM, MB and MS/DBv neurons in in vitro slices; 2) to examine the synaptic organization of brainstem afferents to the SUM and brainstem diencephalic afferents to the MS/DBv at the ultrastructural level; and 3) to examine the effects of ibotenic acid and 192 IgG saporin induced lesions of the MS/DBv on memory, correlating changes in theta to changes in learning and memory. At present, the candidate is very heavily obligated to non-research related activities (i.e., teaching and service). He is seeking a KO2 award to devote more time to research and to develop several new lines of research. Several reports have shown that long-term potentiation (a candidate mechanism for memory) is optimally induced in the hippocampus by stimulation at the theta frequency, and it has been proposed that theta plays a pivotal role in mnemonic processes in the hippocampus. If theta proves to be critical for memory, it is important to fully understand the neural mechanisms responsible for its generation. This work may have important implications for conditions such as Alzheimer's that involve a loss of cholinergic neurons of the MS/DBv.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH001476-05
Application #
6538246
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Program Officer
Anderson, Kathleen C
Project Start
1998-07-01
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2004-06-30
Support Year
5
Fiscal Year
2002
Total Cost
$109,125
Indirect Cost
Name
Florida Atlantic University
Department
Internal Medicine/Medicine
Type
Schools of Arts and Sciences
DUNS #
004147534
City
Boca Raton
State
FL
Country
United States
Zip Code
33431
Morales, George J; Ramcharan, Eion J; Sundararaman, Nithya et al. (2007) Analysis of the actions of nucleus reuniens and the entorhinal cortex on EEG and evoked population behavior of the hippocampus. Conf Proc IEEE Eng Med Biol Soc 2007:2480-4
Vertes, Robert P (2006) Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience 142:1-20
Vertes, Robert P; Hoover, Walter B; Do Valle, Angela Cristina et al. (2006) Efferent projections of reuniens and rhomboid nuclei of the thalamus in the rat. J Comp Neurol 499:768-96
Di Prisco, Gonzalo Viana; Vertes, Robert P (2006) Excitatory actions of the ventral midline thalamus (rhomboid/reuniens) on the medial prefrontal cortex in the rat. Synapse 60:45-55
Vertes, Robert P (2005) Hippocampal theta rhythm: a tag for short-term memory. Hippocampus 15:923-35
Vertes, Robert P; Hoover, Walter B; Viana Di Prisco, Gonzalo (2004) Theta rhythm of the hippocampus: subcortical control and functional significance. Behav Cogn Neurosci Rev 3:173-200
Vertes, Robert P (2004) Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51:32-58
Vertes, Robert P (2004) Memory consolidation in sleep; dream or reality. Neuron 44:135-48
McKenna, James Timothy; Vertes, Robert P (2004) Afferent projections to nucleus reuniens of the thalamus. J Comp Neurol 480:115-42
Viana Di Prisco, Gonzalo; Albo, Zimbul; Vertes, Robert P et al. (2002) Discharge properties of neurons of the median raphe nucleus during hippocampal theta rhythm in the rat. Exp Brain Res 145:383-94

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