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Too Little and Too Much: Hypoactivation and Disinhibition of Medial Prefrontal Cortex Cause Attentional Deficits
- Source :
- Journal of Neuroscience. 34:7931-7946
- Publication Year :
- 2014
- Publisher :
- Society for Neuroscience, 2014.
-
Abstract
- Attentional deficits are core symptoms of schizophrenia, contributing strongly to disability. Prefrontal dysfunction has emerged as a candidate mechanism, with clinical evidence for prefrontal hypoactivation and disinhibition (reduced GABAergic inhibition), possibly reflecting different patient subpopulations. Here, we tested in rats whether imbalanced prefrontal neural activity impairs attention. To induce prefrontal hypoactivation or disinhibition, we microinfused the GABA-A receptor agonist muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side), respectively, into the medial prefrontal cortex. Using the five-choice serial reaction time (5CSRT) test, we showed that both muscimol and picrotoxin impaired attention (reduced accuracy, increased omissions). Muscimol also impaired response control (increased premature responses). In addition, muscimol dose dependently reduced open-field locomotor activity, whereas 300 ng of picrotoxin caused locomotor hyperactivity; sensorimotor gating (startle prepulse inhibition) was unaffected. Therefore, infusion effects on the 5CSRT test can be dissociated from sensorimotor effects. Combining microinfusions with in vivo electrophysiology, we showed that muscimol inhibited prefrontal firing, whereas picrotoxin increased firing, mainly within bursts. Muscimol reduced and picrotoxin enhanced bursting and both drugs changed the temporal pattern of bursting. Picrotoxin also markedly enhanced prefrontal LFP power. Therefore, prefrontal hypoactivation and disinhibition both cause attentional deficits. Considering the electrophysiological findings, this suggests that attention requires appropriately tuned prefrontal activity. Apart from attentional deficits, prefrontal disinhibition caused additional neurobehavioral changes that may be relevant to schizophrenia pathophysiology, including enhanced prefrontal bursting and locomotor hyperactivity, which have been linked to psychosis-related dopamine hyperfunction.
- Subjects :
- Male
Reflex, Startle
Prefrontal Cortex
Choice Behavior
GABA Antagonists
chemistry.chemical_compound
Bursting
Dopamine
Reaction Time
medicine
Animals
Picrotoxin
GABA-A Receptor Agonists
Prefrontal cortex
Prepulse inhibition
Neurons
Sensory gating
Dose-Response Relationship, Drug
Muscimol
musculoskeletal, neural, and ocular physiology
General Neuroscience
Neural Inhibition
Articles
Sensory Gating
Rats
Disease Models, Animal
medicine.anatomical_structure
nervous system
chemistry
Attention Deficit Disorder with Hyperactivity
Disinhibition
Exploratory Behavior
Evoked Potentials, Visual
medicine.symptom
Psychology
Neuroscience
medicine.drug
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....95416f20986e9d2d604658751e01c9bc