Cargando…

Region specific knockdown of Parvalbumin or Somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia

The anterior hippocampus and prefrontal cortex are regions linked to symptoms of schizophrenia. The anterior hippocampus is believed to be a key regulator of the mesolimbic dopamine system and is thought to be the driving force contributing to positive symptoms, while the prefrontal cortex is involv...

Descripción completa

Detalles Bibliográficos
Autores principales: Perez, Stephanie M., Boley, Angela, Lodge, Daniel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803626/
https://www.ncbi.nlm.nih.gov/pubmed/31636253
http://dx.doi.org/10.1038/s41398-019-0603-6
_version_ 1783460982130999296
author Perez, Stephanie M.
Boley, Angela
Lodge, Daniel J.
author_facet Perez, Stephanie M.
Boley, Angela
Lodge, Daniel J.
author_sort Perez, Stephanie M.
collection PubMed
description The anterior hippocampus and prefrontal cortex are regions linked to symptoms of schizophrenia. The anterior hippocampus is believed to be a key regulator of the mesolimbic dopamine system and is thought to be the driving force contributing to positive symptoms, while the prefrontal cortex is involved in cognitive flexibility and negative symptoms. Aberrant activity in these regions is associated with decreases in GABAergic markers, indicative of an interneuron dysfunction. Specifically, selective decreases are observed in interneurons that contain parvalbumin (PV) or somatostatin (SST). Here, we used viral knockdown in rodents to recapitulate this finding and examine the region-specific roles of PV and SST on neuronal activity and behaviors associated with positive, negative and cognitive symptoms. We found that PV and SST had differential effects on neuronal activity and behavior when knocked down in the ventral hippocampus (vHipp) or medial prefrontal cortex (mPFC). Specifically, SST or PV knockdown in the vHipp increased pyramidal cell activity of the region and produced downstream effects on dopamine neuron activity in the ventral tegmental area (VTA). In contrast, mPFC knockdown did not affect the activity of VTA dopamine neuron activity; however, it did produce deficits in negative (social interaction) and cognitive (reversal learning) domains. Taken together, decreases in PV and/or SST were sufficient to produce schizophrenia-like deficits that were dependent on the region targeted.
format Online
Article
Text
id pubmed-6803626
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-68036262019-10-23 Region specific knockdown of Parvalbumin or Somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia Perez, Stephanie M. Boley, Angela Lodge, Daniel J. Transl Psychiatry Article The anterior hippocampus and prefrontal cortex are regions linked to symptoms of schizophrenia. The anterior hippocampus is believed to be a key regulator of the mesolimbic dopamine system and is thought to be the driving force contributing to positive symptoms, while the prefrontal cortex is involved in cognitive flexibility and negative symptoms. Aberrant activity in these regions is associated with decreases in GABAergic markers, indicative of an interneuron dysfunction. Specifically, selective decreases are observed in interneurons that contain parvalbumin (PV) or somatostatin (SST). Here, we used viral knockdown in rodents to recapitulate this finding and examine the region-specific roles of PV and SST on neuronal activity and behaviors associated with positive, negative and cognitive symptoms. We found that PV and SST had differential effects on neuronal activity and behavior when knocked down in the ventral hippocampus (vHipp) or medial prefrontal cortex (mPFC). Specifically, SST or PV knockdown in the vHipp increased pyramidal cell activity of the region and produced downstream effects on dopamine neuron activity in the ventral tegmental area (VTA). In contrast, mPFC knockdown did not affect the activity of VTA dopamine neuron activity; however, it did produce deficits in negative (social interaction) and cognitive (reversal learning) domains. Taken together, decreases in PV and/or SST were sufficient to produce schizophrenia-like deficits that were dependent on the region targeted. Nature Publishing Group UK 2019-10-21 /pmc/articles/PMC6803626/ /pubmed/31636253 http://dx.doi.org/10.1038/s41398-019-0603-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Perez, Stephanie M.
Boley, Angela
Lodge, Daniel J.
Region specific knockdown of Parvalbumin or Somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia
title Region specific knockdown of Parvalbumin or Somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia
title_full Region specific knockdown of Parvalbumin or Somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia
title_fullStr Region specific knockdown of Parvalbumin or Somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia
title_full_unstemmed Region specific knockdown of Parvalbumin or Somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia
title_short Region specific knockdown of Parvalbumin or Somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia
title_sort region specific knockdown of parvalbumin or somatostatin produces neuronal and behavioral deficits consistent with those observed in schizophrenia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803626/
https://www.ncbi.nlm.nih.gov/pubmed/31636253
http://dx.doi.org/10.1038/s41398-019-0603-6
work_keys_str_mv AT perezstephaniem regionspecificknockdownofparvalbuminorsomatostatinproducesneuronalandbehavioraldeficitsconsistentwiththoseobservedinschizophrenia
AT boleyangela regionspecificknockdownofparvalbuminorsomatostatinproducesneuronalandbehavioraldeficitsconsistentwiththoseobservedinschizophrenia
AT lodgedanielj regionspecificknockdownofparvalbuminorsomatostatinproducesneuronalandbehavioraldeficitsconsistentwiththoseobservedinschizophrenia