We have previously demonstrated that the nucleus pontis oralis (RPO) and the median raphe nucleus are directly involved in the synchronization (theta rhythm) and desynchronization of the hippocampal EEG, respectively, and that the suprammillary nucleus serves as a critical relay between RPO and the septum/hippocampus in the control of the theta rhythm. In recent work, we have shown that cells in several structures of """"""""Papez's circuit"""""""" fire rhythmically with theta including the mammillary bodies, the ventral tegmental nucleus of Gudden and the anterior ventral nucleus of the thalamus. This suggests that a theta rhythmic signal may resonate throughout Papez's circuit, possibly involved in mnemonic functions of the circuit. The proposed studies will involve three main areas: ascending theta synchronizing systems, ascending hippocampal desynchronizing systems and theta output systems from the hippocampus. Theta synchronizing structures include the supramammillary nucleus and nucleus reuniens of the thalamus; desynchronizing structures include the median raphe nucleus, and theta output structures include the anterior ventral nucleus of thalamus, the presubiculum and the retrosplenial cortex. We will: (1) describe the neurochemical identity of cells together with their physiological profiles using juxtacellular labeling techniques; (2) examine the activity of cells in anesthetized and freely moving rats with respect to the hippocampal EEG; (3) examine the anatomical projections of cells including transmitter specific projections at the light and electron microscopic level; and (4) examine overall patterns of glucose utilization throughout the brain following continuous theta using the 2-DG technique. With this series of studies, we intend to fully characterize systems involved in the generation of theta and those that block its expression in the hippocampus (hippocampal EEG desynchronization) as well as define theta-mediated actions of the hippocampus on extra-hippocampal structures, primarily those of the limbic system and Papez's circuit. An accumulating body of evidence, including several recent reports showing task related theta activity in humans, indicates that the theta rhythm serves a critical role in memory. If, as indicated, theta proves to be critical for memory, we believe it is vitally important to fully understand the neural mechanisms responsible for the generation of theta as well as its actions on other regions of the brain. This work may have important implications for disorders of memory including Korsakoff's syndrome, diencephalic amnesia and Alzheimer's disease.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-7 (02))
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Anderson, Kathleen C
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Florida Atlantic University
Internal Medicine/Medicine
Schools of Arts and Sciences
Boca Raton
United States
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Vertes, Robert P; Hoover, Walter B (2008) Projections of the paraventricular and paratenial nuclei of the dorsal midline thalamus in the rat. J Comp Neurol 508:212-37
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
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