The PI has been involved in neuroscience research since 1980 and is currently a full-time faculty member at Dartmouth College. The PI wishes to develop a strong research career in behavioral/system neuroscience and make significant contributions to his field. His areas of interests center on the neurobiological mechanisms underlying higher cognitive processes in mammals, in particular learning/memory and spatial cognition. He currently has 5 full-time students in his laboratory. This award will provide relief from several teaching responsibilities and enable him to focus more time on his research and train students within the laboratory. The Award will also provide time for him to learn several new research techniques related to his studies and develop new venues of research interest. Dartmouth College has committed significant financial resources to Dr. Taube over the next 10 years and wants him to develop a strong neuroscience program at the College. Dartmouth College and its affiliated Medical School have all the resources necessary for Dr. Taube to pursue his research goals. The Research Plan describes a series of experiments which will examine how spatial information is process in the mammalian brain. In previous studies a population of neurons was identified within the hippocampal formation and anterior thalamic nuclei which discharge as a function of the animal's head direction, independent of the animal's behavior and spatial location. This spatial signal provides a model system for examining how primary sensory information, entering through various sensory pathways, is transformed into a """"""""higher level cognitive signal"""""""" representing the organism's spatial relationship with its environment. The mechanisms which accomplish this transformation in the central nervous system are not known.
The first aim of the proposal is to examine how the head direction (HD) cell signal is processed in the brain. To address this issue, four experimental approaches are pursued: anatomical, single-unit recordings, lesion studies, and electrical stimulation. A second line of investigation will focus on how animals use HD cells in behavior and spatial navigation. To date, head direction cell activity has been recorded only in rats moving freely in a cylindrical environment retrieving food pellets. The proposed studies will evaluate how different behavioral paradigms affect head direction cell activity. Additional experiments will determine l) whether HD cells require volitional motor input for activation, 2) the role of GABAergic interneurons in defining the HD cell's """"""""tuning curve"""""""", and 3) the role of NMDA receptors in establishing an animal's spatial orientation in a novel environment. Finally the contributions of vestibular, kinesthetic, optic flow, and motor efferent copy cues on HD cell activity will be assessed. The results from the proposed experiments will provide insight into how spatial information is processed in the brain and have implications for human health and behavior. It is common for elderly patients and patients with Alzheimer's disease, a disease often associated with marked pathology in limbic system structures, to experience spatial disorientation to the extent that constant supervision is required. Learning how spatial information is processed in the rat brain will give us clues about the complex nature of spatial processes in humans.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research (K02)
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Cognitive Functional Neuroscience Review Committee (CFN)
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Dartmouth College
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Taube, Jeffrey S; Wang, Sarah S; Kim, Stanley Y et al. (2013) Updating of the spatial reference frame of head direction cells in response to locomotion in the vertical plane. J Neurophysiol 109:873-88
Taube, Jeffrey S (2010) Interspike interval analyses reveal irregular firing patterns at short, but not long, intervals in rat head direction cells. J Neurophysiol 104:1635-48
Calton, Jeffrey L; Turner, Carol S; Cyrenne, De-Laine M et al. (2008) Landmark control and updating of self-movement cues are largely maintained in head direction cells after lesions of the posterior parietal cortex. Behav Neurosci 122:827-40
Bassett, Joshua P; Tullman, Matthew L; Taube, Jeffrey S (2007) Lesions of the tegmentomammillary circuit in the head direction system disrupt the head direction signal in the anterior thalamus. J Neurosci 27:7564-77
Calton, Jeffrey L; Taube, Jeffrey S (2005) Degradation of head direction cell activity during inverted locomotion. J Neurosci 25:2420-8
Bassett, Joshua P; Zugaro, Michael B; Muir, Gary M et al. (2005) Passive movements of the head do not abolish anticipatory firing properties of head direction cells. J Neurophysiol 93:1304-16
Muir, Gary M; Taube, Jeffrey S (2004) Head direction cell activity and behavior in a navigation task requiring a cognitive mapping strategy. Behav Brain Res 153:249-53
Taube, Jeffrey S; Stackman, Robert W; Calton, Jeffrey L et al. (2004) Rat head direction cell responses in zero-gravity parabolic flight. J Neurophysiol 92:2887-997
Stackman, Robert W; Golob, Edward J; Bassett, Joshua P et al. (2003) Passive transport disrupts directional path integration by rat head direction cells. J Neurophysiol 90:2862-74
Taube, Jeffrey S; Bassett, Joshua P (2003) Persistent neural activity in head direction cells. Cereb Cortex 13:1162-72

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