Phencyclidine discoordinates hippocampal network activity but not place fields
Preprint
- 9 October 2017
- preprint
- other
- Published by Cold Spring Harbor Laboratory
- p. 200162
- https://doi.org/10.1101/200162
Abstract
We used the psychotomimetic phencyclidine (PCP) to investigate the relationships between cognitive behavior, coordinated neural network function and information processing within the hippocampus place cell system. We report in rats that PCP (5mg/kg i.p.) impairs a well-learned hippocampus-dependent place avoidance behavior in rats that requires cognitive control, even when PCP is injected directly into dorsal hippocampus. PCP increases 60-100 Hz medium gamma oscillations in hippocampus CA1 and these increases correlate with the cognitive impairment caused by systemic PCP administration. PCP discoordinates theta-modulated medium and slow gamma oscillations in CA1 local field potentials (LFP) such that medium gamma oscillations become more theta-organized than slow gamma oscillations. CA1 place cell firing fields are preserved under PCP but the drug discoordinates the sub-second temporal organization of discharge amongst place cells. This discoordination causes place cell ensemble representations of a familiar space to cease resembling pre-PCP representations, despite preserved place fields. These findings point to the cognitive impairments caused by PCP arising from neural discoordination. PCP disrupts the timing of discharge with respect to the sub-second timescales of theta and gamma oscillations in the LFP. Because these oscillations arise from local inhibitory synaptic activity, these findings point to excitation-inhibition discoordination as the root of PCP-induced cognitive impairment.SIGNIFICANCE STATEMENT: Hippocampal neural discharge is temporally coordinated on timescales of theta and gamma oscillations in the local field potential, and the discharge of a subset of pyramidal neurons called “place cells” is spatially organized such that discharge is restricted to locations called a cell’s “place field.” Because this temporal coordination and spatial discharge organization is thought to represent spatial knowledge, we used the psychotomimetic phencyclidine (PCP) to disrupt cognitive behavior and assess the importance of neural coordination and place fields for spatial cognition. PCP impaired the judicious use of spatial information and discoordinated hippocampal discharge, without disrupting firing fields. These findings dissociate place fields from spatial cognitive behavior and suggest that hippocampus discharge coordination is crucial to spatial cognition.Keywords
Other Versions
- Published version: Version Journal of Neuroscience, 37, preprints
This publication has 89 references indexed in Scilit:
- Slow and Fast Gamma Rhythms Coordinate Different Spatial Coding Modes in Hippocampal Place CellsNeuron, 2014
- Dissecting spatial knowledge from spatial choice by hippocampal NMDA receptor deletionNature Neuroscience, 2012
- Cross-Frequency Phase–Phase Coupling between Theta and Gamma Oscillations in the HippocampusJournal of Neuroscience, 2012
- The drugs don’t work—or do they? Pharmacological and transgenic studies of the contribution of NMDA and GluR-A-containing AMPA receptors to hippocampal-dependent memoryPsychopharmacology, 2006
- Corticolimbic Dopamine Neurotransmission Is Temporally Dissociated from the Cognitive and Locomotor Effects of PhencyclidineJournal of Neuroscience, 1998
- The NMDA Antagonist Model for Schizophrenia: Promise and PitfallsPharmacopsychiatry, 1998
- Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteersAmerican Journal of Psychiatry, 1997
- Distinct components of spatial learning revealed by prior training and NMDA receptor blockadeNature, 1995
- N-methyl-d-aspartate transmission modulates GABAB-mediated inhibition of rat hippocampal pyramidal neurons in vitroNeuroscience, 1995
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartateBritish Journal of Pharmacology, 1983