NMDA receptors on parvalbumin-positive interneurons and pyramidal neurons both contribute to MK-801 induced gamma oscillatory disturbances: Complex relationships with behaviour

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Abstract

Background: NMDAr antagonists induce disturbances to gamma frequency oscillations, including increasing ongoing gamma activity and reducing evoked gamma oscillations. We sought to investigate the role parvalbumin (PV+) neurons and CaMKIIα+ pyramidal cells in NMDAr antagonist-induced disturbances in gamma oscillatory activity and relate these to common behavioural consequences of these drugs by selectively deleting the obligatory GluN1 subunit from these cells in mice. Methods: Adult mice (total n = 99) with GluN1 deleted from PV interneurons (PV:GluN1 KO) or CaMKIIα+ pyramidal cells (CaMKIIα:GluN1 KO), and WT littermates, were used. We assessed effects of the NMDAr antagonist MK-801 on prepulse inhibition (PPI) and locomotor behaviour. Then, mice were implanted with electrodes in the prefrontal cortex (mPFC) and hippocampus (dHPC), and the effects of MK-801 on gamma oscillations assessed. Results: In WT mice, MK-801 increased ongoing gamma power, reduced evoked gamma power and increased gamma coherence. These changes were accompanied by hyperlocomotion and deficient PPI. The consequences of NMDAr antagonism were differentially regulated in the transgenic mice. The MK-801-induced increase in ongoing gamma power was significantly attenuated in both transgenic strains, but deficits to evoked gamma activity were unaffected by genotype. Deficient PPI was not affected by genotype, and only in PV:GluN1 KO mice was the hyperlocomotor phenotype of MK-801 attenuated. The emergence of abnormal gamma band hyperconnectivity between the mPFC and dHPC was absent in CaMKIIα:GluN1 KO mice. Conclusion: This study suggests that the effects of NMDAr antagonism on gamma band responses and behaviour have complex relationships, and rely on different populations of neurons.

Original languageEnglish
Article number104625
Number of pages13
JournalNeurobiology of Disease
Volume134
DOIs
Publication statusPublished - 1 Feb 2020

Keywords

  • Behaviour
  • Electrophysiology
  • Gamma oscillations
  • Mice
  • NMDA receptor antagonism
  • Parvalbumin interneurons
  • Schizophrenia

Cite this

@article{46ca34145b2c42058cb9fbe91a7f8d8d,
title = "NMDA receptors on parvalbumin-positive interneurons and pyramidal neurons both contribute to MK-801 induced gamma oscillatory disturbances: Complex relationships with behaviour",
abstract = "Background: NMDAr antagonists induce disturbances to gamma frequency oscillations, including increasing ongoing gamma activity and reducing evoked gamma oscillations. We sought to investigate the role parvalbumin (PV+) neurons and CaMKIIα+ pyramidal cells in NMDAr antagonist-induced disturbances in gamma oscillatory activity and relate these to common behavioural consequences of these drugs by selectively deleting the obligatory GluN1 subunit from these cells in mice. Methods: Adult mice (total n = 99) with GluN1 deleted from PV interneurons (PV:GluN1 KO) or CaMKIIα+ pyramidal cells (CaMKIIα:GluN1 KO), and WT littermates, were used. We assessed effects of the NMDAr antagonist MK-801 on prepulse inhibition (PPI) and locomotor behaviour. Then, mice were implanted with electrodes in the prefrontal cortex (mPFC) and hippocampus (dHPC), and the effects of MK-801 on gamma oscillations assessed. Results: In WT mice, MK-801 increased ongoing gamma power, reduced evoked gamma power and increased gamma coherence. These changes were accompanied by hyperlocomotion and deficient PPI. The consequences of NMDAr antagonism were differentially regulated in the transgenic mice. The MK-801-induced increase in ongoing gamma power was significantly attenuated in both transgenic strains, but deficits to evoked gamma activity were unaffected by genotype. Deficient PPI was not affected by genotype, and only in PV:GluN1 KO mice was the hyperlocomotor phenotype of MK-801 attenuated. The emergence of abnormal gamma band hyperconnectivity between the mPFC and dHPC was absent in CaMKIIα:GluN1 KO mice. Conclusion: This study suggests that the effects of NMDAr antagonism on gamma band responses and behaviour have complex relationships, and rely on different populations of neurons.",
keywords = "Behaviour, Electrophysiology, Gamma oscillations, Mice, NMDA receptor antagonism, Parvalbumin interneurons, Schizophrenia",
author = "Hudson, {Matthew R.} and Elysia Sokolenko and O'Brien, {Terence J.} and Jones, {Nigel C.}",
year = "2020",
month = "2",
day = "1",
doi = "10.1016/j.nbd.2019.104625",
language = "English",
volume = "134",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Elsevier",

}

TY - JOUR

T1 - NMDA receptors on parvalbumin-positive interneurons and pyramidal neurons both contribute to MK-801 induced gamma oscillatory disturbances

T2 - Complex relationships with behaviour

AU - Hudson, Matthew R.

AU - Sokolenko, Elysia

AU - O'Brien, Terence J.

AU - Jones, Nigel C.

PY - 2020/2/1

Y1 - 2020/2/1

N2 - Background: NMDAr antagonists induce disturbances to gamma frequency oscillations, including increasing ongoing gamma activity and reducing evoked gamma oscillations. We sought to investigate the role parvalbumin (PV+) neurons and CaMKIIα+ pyramidal cells in NMDAr antagonist-induced disturbances in gamma oscillatory activity and relate these to common behavioural consequences of these drugs by selectively deleting the obligatory GluN1 subunit from these cells in mice. Methods: Adult mice (total n = 99) with GluN1 deleted from PV interneurons (PV:GluN1 KO) or CaMKIIα+ pyramidal cells (CaMKIIα:GluN1 KO), and WT littermates, were used. We assessed effects of the NMDAr antagonist MK-801 on prepulse inhibition (PPI) and locomotor behaviour. Then, mice were implanted with electrodes in the prefrontal cortex (mPFC) and hippocampus (dHPC), and the effects of MK-801 on gamma oscillations assessed. Results: In WT mice, MK-801 increased ongoing gamma power, reduced evoked gamma power and increased gamma coherence. These changes were accompanied by hyperlocomotion and deficient PPI. The consequences of NMDAr antagonism were differentially regulated in the transgenic mice. The MK-801-induced increase in ongoing gamma power was significantly attenuated in both transgenic strains, but deficits to evoked gamma activity were unaffected by genotype. Deficient PPI was not affected by genotype, and only in PV:GluN1 KO mice was the hyperlocomotor phenotype of MK-801 attenuated. The emergence of abnormal gamma band hyperconnectivity between the mPFC and dHPC was absent in CaMKIIα:GluN1 KO mice. Conclusion: This study suggests that the effects of NMDAr antagonism on gamma band responses and behaviour have complex relationships, and rely on different populations of neurons.

AB - Background: NMDAr antagonists induce disturbances to gamma frequency oscillations, including increasing ongoing gamma activity and reducing evoked gamma oscillations. We sought to investigate the role parvalbumin (PV+) neurons and CaMKIIα+ pyramidal cells in NMDAr antagonist-induced disturbances in gamma oscillatory activity and relate these to common behavioural consequences of these drugs by selectively deleting the obligatory GluN1 subunit from these cells in mice. Methods: Adult mice (total n = 99) with GluN1 deleted from PV interneurons (PV:GluN1 KO) or CaMKIIα+ pyramidal cells (CaMKIIα:GluN1 KO), and WT littermates, were used. We assessed effects of the NMDAr antagonist MK-801 on prepulse inhibition (PPI) and locomotor behaviour. Then, mice were implanted with electrodes in the prefrontal cortex (mPFC) and hippocampus (dHPC), and the effects of MK-801 on gamma oscillations assessed. Results: In WT mice, MK-801 increased ongoing gamma power, reduced evoked gamma power and increased gamma coherence. These changes were accompanied by hyperlocomotion and deficient PPI. The consequences of NMDAr antagonism were differentially regulated in the transgenic mice. The MK-801-induced increase in ongoing gamma power was significantly attenuated in both transgenic strains, but deficits to evoked gamma activity were unaffected by genotype. Deficient PPI was not affected by genotype, and only in PV:GluN1 KO mice was the hyperlocomotor phenotype of MK-801 attenuated. The emergence of abnormal gamma band hyperconnectivity between the mPFC and dHPC was absent in CaMKIIα:GluN1 KO mice. Conclusion: This study suggests that the effects of NMDAr antagonism on gamma band responses and behaviour have complex relationships, and rely on different populations of neurons.

KW - Behaviour

KW - Electrophysiology

KW - Gamma oscillations

KW - Mice

KW - NMDA receptor antagonism

KW - Parvalbumin interneurons

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=85076164054&partnerID=8YFLogxK

U2 - 10.1016/j.nbd.2019.104625

DO - 10.1016/j.nbd.2019.104625

M3 - Article

AN - SCOPUS:85076164054

VL - 134

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

M1 - 104625

ER -