title: Excitatory Inputs Determine Phase-Locking Strength and Spike-Timing of CA1 Stratum Oriens/Alveus Parvalbumin and Somatostatin Interneurons during Intrinsically Generated Hippocampal Theta Rhythm.
abstract: Theta oscillations are essential for learning and memory, and their generation requires GABAergic interneurons. To better understand how theta is generated, we explored how parvalbumin (PV) and somatostatin (SOM) interneurons in CA1 stratum oriens/alveus fire during hippocampal theta and investigated synaptic mechanisms underlying their behavior. Combining the use of transgenic mice to visually identify PV and SOM interneurons and the intact hippocampal preparation that can generate theta oscillations in vitro without cholinergic agonists, we performed simultaneous field and whole-cell recordings. We found that PV interneurons uniformly fire strongly phase-locked to theta, whereas SOM neurons are more heterogeneous with only a proportion of cells displaying tight phase-locking. Differences in phase-locking strength could be explained by disparity in excitatory inputs received; PV neurons received significantly larger EPSCs compared with SOM neurons, and the degree of phase-locking in SOM neurons was significantly correlated with the size of EPSCs. In contrast, IPSC amplitude did not differ between cell types. We determined that the local CA1 rhythm plays a more dominant role in driving CA1 interneuron firing than afferent inputs from the CA3. Last, we show that PV and strongly phase-locked SOM neurons fire near the peak of CA1 theta, under the tight control of excitatory inputs that arise at a specific phase of each theta cycle. These results reveal a fundamental mechanism of neuronal phase-locking and highlight an important role of excitation from the local network in governing firing behavior during rhythmic network states.
  
  
  
  Rhythmic activity in the theta range (3-12 Hz) is important for proper functioning of the hippocampus, a brain area essential for learning and memory. To understand how theta rhythm is generated, we investigated how two types of inhibitory neurons, those that express parvalbumin and somatostatin, fire action potentials during theta in an in vitro preparation of the mouse hippocampus. We found that the amount of excitatory input they receive from the local network determines how closely their spikes follow the network theta rhythm. Our findings reveal an important role of local excitatory input in driving inhibitory neuron firing during rhythmic states and may have implications for diseases, such as epilepsy and Alzheimer's disease, which affect the hippocampus and related areas.
authors.affiliation: Douglas Mental Health University Institute, Montreal, Quebec H4H 1R3, Canada, Integrated Program in Neuroscience, McGill University, Montreal, Quebec H4H 1R3, Canada.
authors.forename: Carey Y L
authors.identifier: 0000-0002-1405-294X
authors.initials: CY
authors.lastname: Huh
authors.affiliation: Douglas Mental Health University Institute, Montreal, Quebec H4H 1R3, Canada, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Amilhon
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada, Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada.
authors.forename: Katie A
authors.initials: KA
authors.lastname: Ferguson
authors.affiliation: Douglas Mental Health University Institute, Montreal, Quebec H4H 1R3, Canada, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada.
authors.forename: Frédéric
authors.identifier: 0000-0003-3725-9561
authors.initials: F
authors.lastname: Manseau
authors.affiliation: Douglas Mental Health University Institute, Montreal, Quebec H4H 1R3, Canada, Integrated Program in Neuroscience, McGill University, Montreal, Quebec H4H 1R3, Canada.
authors.forename: Susana G
authors.initials: SG
authors.lastname: Torres-Platas
authors.affiliation: Department of Mechanical and Industrial Engineering, Concordia University, Montreal, Quebec H4B 1R6, Canada.
authors.forename: John P
authors.identifier: 0000-0003-2713-0326
authors.initials: JP
authors.lastname: Peach
authors.affiliation: Douglas Mental Health University Institute, Montreal, Quebec H4H 1R3, Canada, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Scodras
authors.affiliation: Douglas Mental Health University Institute, Montreal, Quebec H4H 1R3, Canada, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada, Integrated Program in Neuroscience, McGill University, Montreal, Quebec H4H 1R3, Canada.
authors.forename: Naguib
authors.initials: N
authors.lastname: Mechawar
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada, Department of Medicine (Neurology) and Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada, and.
authors.forename: Frances K
authors.initials: FK
authors.lastname: Skinner
authors.affiliation: Douglas Mental Health University Institute, Montreal, Quebec H4H 1R3, Canada, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada, Integrated Program in Neuroscience, McGill University, Montreal, Quebec H4H 1R3, Canada, sylvain.williams@gmail.com.
authors.forename: Sylvain
authors.identifier: 0000-0002-2511-0631
authors.initials: S
authors.lastname: Williams
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D007395:Interneurons / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D055366:Synaptic Potentials / Q000235:genetics / Q000502:physiology; D013826:Theta Rhythm / Q000502:physiology*
chemical_list: D010320:Parvalbumins; D013004:Somatostatin
keywords: hippocampus; interneurons; neural oscillations; parvalbumin; somatostatin; theta rhythm