Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 97, Issue 14, Pages 8128-8133Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.100124097
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Funding
- NIGMS NIH HHS [R01 GM055719] Funding Source: Medline
- NIMH NIH HHS [MH 47150] Funding Source: Medline
- NINDS NIH HHS [R56 NS034425, NS 34425, R29 NS034425, R01 NS034425] Funding Source: Medline
- PHS HHS [DMS 9631755] Funding Source: Medline
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During active exploration, hippocampal neurons exhibit nested rhythmic activity at theta (approximate to 8 Hz) and gamma (approximate to 40 Hz) frequencies. Gamma rhythms may be generated locally by interactions within a class of interneurons mediating fast GABA(A) (GABA(A,fast)) inhibitory postsynaptic currents (IPSCs), whereas theta rhythms traditionally are thought to be imposed extrinsically, However, the hippocampus contains slow biophysical mechanisms that may contribute to the theta rhythm, either as a resonance activated by extrinsic input or as a purely local phenomenon. For example, region CA1 of the hippocampus contains a slower class of GABA(A) (GABA(A,slow)) synapses, believed to be generated by a distinct group of interneurons. Recent evidence indicates that these GABA(A,slow) interneurons project to the GABA(A,fast) interneurons that contribute to hippocampal gamma rhythms. Here, we use biophysically based simulations to explore the possible ramifications of interneuronal circuits containing separate classes of GABA(A,fast) and GABA(A,slow) interneurons. Simulated interneuronal networks with fast and slow synaptic kinetics can generate mixed theta-gamma rhythmicity under restricted conditions, including strong connections among each population, weaker connections between the two populations, and homogeneity of cellular properties and drive. Under a broader range of conditions, including heterogeneity, the networks can amplify and resynchronize phasic responses to weak phase-dispersed external drive at theta frequencies to either GABA(A,slow) or GABA(A,fast) cells. GABA(A,slow) synapses are necessary for this process of amplification and resynchronization.
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