TY - JOUR

T1 - Glutamatergic regulation of cognition and functional brain connectivity

T2 - insights from pharmacological, genetic and translational schizophrenia research

AU - Dauvermann, Maria R.

AU - Lee, Graham

AU - Dawson, Neil

N1 - This is the peer reviewed version of the following article: Dauvermann, M. R., Lee, G., and Dawson, N. (2017) Glutamatergic regulation of cognition and functional brain connectivity: insights from pharmacological, genetic and translational schizophrenia research. British Journal of Pharmacology, 174: 3136–3160. doi: 10.1111/bph.13919 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/bph.13919/abstract This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

PY - 2017/10

Y1 - 2017/10

N2 - The pharmacological modulation of glutamatergic neurotransmission to improve cognitive function has been a focus of intensive research, particularly in relation to the cognitive deficits seen in schizophrenia. Despite this effort there has been little success in the clinical use of glutamatergic compounds as procognitive drugs. Here we review a selection of the drugs used to modulate glutamatergic signalling and how they impact on cognitive function in rodents and humans. We highlight how glutamatergic dysfunction, and NMDA receptor hypofunction in particular, is a key mechanism contributing to the cognitive deficits observed in schizophrenia, and outline some of the glutamatergic targets that have been tested as putative procognitive targets for the disorder. Using translational research in this area as a leading exemplar, namely models of NMDA receptor hypofunction, we discuss how the study of functional brain network connectivity can provide new insight into how the glutamatergic system impacts on cognitive function. Future studies characterising functional brain network connectivity will increase our understanding of how glutamatergic compounds regulate cognition and could contribute to the future success of glutamatergic drug validation.

AB - The pharmacological modulation of glutamatergic neurotransmission to improve cognitive function has been a focus of intensive research, particularly in relation to the cognitive deficits seen in schizophrenia. Despite this effort there has been little success in the clinical use of glutamatergic compounds as procognitive drugs. Here we review a selection of the drugs used to modulate glutamatergic signalling and how they impact on cognitive function in rodents and humans. We highlight how glutamatergic dysfunction, and NMDA receptor hypofunction in particular, is a key mechanism contributing to the cognitive deficits observed in schizophrenia, and outline some of the glutamatergic targets that have been tested as putative procognitive targets for the disorder. Using translational research in this area as a leading exemplar, namely models of NMDA receptor hypofunction, we discuss how the study of functional brain network connectivity can provide new insight into how the glutamatergic system impacts on cognitive function. Future studies characterising functional brain network connectivity will increase our understanding of how glutamatergic compounds regulate cognition and could contribute to the future success of glutamatergic drug validation.

U2 - 10.1111/bph.13919

DO - 10.1111/bph.13919

M3 - Journal article

C2 - 28626937

VL - 174

SP - 3136

EP - 3160

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 19

ER -