Intrinsic Mechanisms of Frequency Selectivity in the Proximal Dendrites of CA1 Pyramidal Neurons

J Neurosci. 2018 Sep 19;38(38):8110-8127. doi: 10.1523/JNEUROSCI.0449-18.2018. Epub 2018 Aug 3.

Abstract

Gamma oscillations are thought to play a role in learning and memory. Two distinct bands, slow (25-50 Hz) and fast (65-100 Hz) gamma, have been identified in area CA1 of the rodent hippocampus. Slow gamma is phase locked to activity in area CA3 and presumably driven by the Schaffer collaterals (SCs). We used a combination of computational modeling and in vitro electrophysiology in hippocampal slices of male rats to test whether CA1 neurons responded to SC stimulation selectively at slow gamma frequencies and to identify the mechanisms involved. Both approaches demonstrated that, in response to temporally precise input at SCs, CA1 pyramidal neurons fire preferentially in the slow gamma range regardless of whether the input is at fast or slow gamma frequencies, suggesting frequency selectivity in CA1 output with respect to CA3 input. In addition, phase locking, assessed by the vector strength, was more precise for slow gamma than fast gamma input. This frequency selectivity was greatly attenuated when the slow Ca2+-dependent K+ (SK) current was removed from the model or blocked in vitro with apamin. Perfusion of slices with BaCl2 to block A-type K+ channels tightened this frequency selectivity. Both the broad-spectrum cholinergic agonist carbachol and the muscarinic agonist oxotremorine-M greatly attenuated the selectivity. The more precise firing at slower frequencies persisted throughout all of the pharmacological manipulations conducted. We propose that these intrinsic mechanisms provide a means by which CA1 phase locks to CA3 at different gamma frequencies preferentially in vivo as physiological conditions change with behavioral demands.SIGNIFICANCE STATEMENT Gamma frequency activity, one of multiple bands of synchronous activity, has been suggested to underlie various aspects of hippocampal function. Multisite recordings within the rat hippocampal formation indicate that different behavioral tasks are associated with synchronized activity between areas CA3 and CA1 at two different gamma bands: slow and fast gamma. In this study, we examine the intrinsic mechanisms that may allow CA1 to selectively "listen" to CA3 at slow compared with fast gamma and suggest mechanisms that gate this selectivity. Identifying the intrinsic mechanisms underlying differential gamma preference may help to explain the distinct types of CA3-CA1 synchronization observed in vivo under different behavioral conditions.

Keywords: dendrite; synaptic transmission; synchronization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiology*
  • Carbachol / pharmacology
  • Cholinergic Agonists / pharmacology
  • Dendrites / drug effects
  • Dendrites / physiology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Gamma Rhythm / drug effects
  • Gamma Rhythm / physiology*
  • Male
  • Models, Neurological*
  • Potassium Channel Blockers / pharmacology
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Rats
  • Synapses / drug effects
  • Synapses / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Cholinergic Agonists
  • Potassium Channel Blockers
  • Carbachol