Rhythms of the nervous system have been linked to important behavioral and cognitive states, including attention, working memory, associative memory, bottom-up feature binding, object recognition, sensory motor integration, perception and language processing. Pathologies in the rhythms have been linked to schizophrenia and Alzheimer's disease. Although these rhythms have been detected both in vitro and in vivo, how they participate in cognition is still not understood. The general aim of this proposal is to make use of biophysical information about cells and synapses in modeling studies to understand the origin and mechanisms of coherence of the various rhythms displayed in nervous system. Some of this information exists from previous experiments. Other data will be gathered in experiments proposed here. The proposal focuses on three important rhythms: gamma (30-80 Hz), beta (12-30 Hz) and theta (4-11 Hz). A major goal of this work is to understand how the mechanisms that produce the rhythms influence the way the nervous system processes structured input. There are many experimental paradigms that produce different versions of rhythms with the same frequency range. These are analogues of different in vivo situations, and can have different reactions to pharmacological perturbations. In different versions of the same frequency rhythm, there are different synaptic conductances that are critical and there may be different classes of interneurons participating. The modeling aims to probe the roles of the different intrinsic and synaptic currents in producing the individual rhythms and the interactions among them, including nesting rhythms and the transitions among them that are associated with changes of behavioral state. Experiments, done in tandem, aim to reveal more details of the electrophysiological and pharmacological properties of the classes of interneurons, and roles of electrical synapses in producing rhythms. There will also be experiments aimed at teasing out different rhythms in different layers of the neocortex. Other experimental paradigms will probe effects of sensory stimuli, the importance of synaptic plasticity in the transformation among rhythms, and the conditions under which nesting of gamma and theta occur. We will also study, both experimentally and via modeling, separated networks that produce a coherent gamma rhythm, and networks distributed over space. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS046058-04
Application #
6941594
Study Section
Special Emphasis Panel (ZRG1-IFCN-5 (50))
Program Officer
Liu, Yuan
Project Start
2002-09-30
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2007-08-31
Support Year
4
Fiscal Year
2005
Total Cost
$327,089
Indirect Cost
Name
Boston University
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Wulff, Peer; Ponomarenko, Alexey A; Bartos, Marlene et al. (2009) Hippocampal theta rhythm and its coupling with gamma oscillations require fast inhibition onto parvalbumin-positive interneurons. Proc Natl Acad Sci U S A 106:3561-6
Kramer, Mark A; Roopun, Anita K; Carracedo, Lucy M et al. (2008) Rhythm generation through period concatenation in rat somatosensory cortex. PLoS Comput Biol 4:e1000169
Borgers, Christoph; Epstein, Steven; Kopell, Nancy J (2008) Gamma oscillations mediate stimulus competition and attentional selection in a cortical network model. Proc Natl Acad Sci U S A 105:18023-8
Borgers, Christoph; Kopell, Nancy J (2008) Gamma oscillations and stimulus selection. Neural Comput 20:383-414
Silver, Rae; Boahen, Kwabena; Grillner, Sten et al. (2007) Neurotech for neuroscience: unifying concepts, organizing principles, and emerging tools. J Neurosci 27:11807-19
Hamzei-Sichani, Farid; Kamasawa, Naomi; Janssen, William G M et al. (2007) Gap junctions on hippocampal mossy fiber axons demonstrated by thin-section electron microscopy and freeze fracture replica immunogold labeling. Proc Natl Acad Sci U S A 104:12548-53
Dugladze, Tamar; Vida, Imre; Tort, Adriano B et al. (2007) Impaired hippocampal rhythmogenesis in a mouse model of mesial temporal lobe epilepsy. Proc Natl Acad Sci U S A 104:17530-5
Tort, Adriano B L; Rotstein, Horacio G; Dugladze, Tamar et al. (2007) On the formation of gamma-coherent cell assemblies by oriens lacunosum-moleculare interneurons in the hippocampus. Proc Natl Acad Sci U S A 104:13490-5
Soto, Gabriel; Kopell, Nancy; Sen, Kamal (2006) Network architecture, receptive fields, and neuromodulation: computational and functional implications of cholinergic modulation in primary auditory cortex. J Neurophysiol 96:2972-83
Rotstein, Horacio G; Oppermann, Tim; White, John A et al. (2006) The dynamic structure underlying subthreshold oscillatory activity and the onset of spikes in a model of medial entorhinal cortex stellate cells. J Comput Neurosci 21:271-92

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