Acute systemic MK-801 induced functional uncoupling between hippocampal areas CA3 and CA1 with distant effect in the retrosplenial cortex.
The hippocampus and retrosplenial cortex are integrated within a higher-order cognitive circuit supporting relational (spatial, contextual, episodic) forms of learning and memory. Hippocampal place cells can coordinate multiple parallel representations in the same physical environment. Novel environment exploration triggers expression of immediate-early genes (IEGs) Arc and Homer1a in spatial context-specific ensembles of CA1 and CA3 neurons. Less is know about ensemble coding in the retrosplenial cortex (RSC), a region directly connected and functionally coupled to CA1. Hippocampal and retrosplenial damage is found in patients with schizophrenia alongside cognitive deficits affecting relational memory. Systemic administration of non-competitive NMDAR antagonists such as MK-801 is used to model psychosis in animals and humans. Acute systemic MK-801 (0.15 mg/kg) impaired cognitive control in rats and ensemble code for spatial context in CA1. Here, we use expression of immediate-early genes Arc and Homer 1a to examine ensemble coding in rat CA3 and RSC to test if the effect of MK-801 extends upstream and downstream of CA1, respectively. Different rats explored the same context twice (A/A), explored two distinct contexts (A/B) or remained in their home cage (CC). In contrast to CA1, MK-801 did not affect ensemble coding in CA3. Unlike CA3 and CA1, similarity of RSC ensembles active during exploration did not reflect change in spatial context, but MK-801 (0.15 mg/kg) increased similarity in RSC ensembles active during spontaneous behavior in the home cage. The data provide support for MK-801-induced functional uncoupling between CA3 and CA1 and suggest that ensemble coding deficit may extend downstream of CA1. This deficit may reflect hyperassociative state in the cognitive circuit underlying cognitive disorganization in psychosis. © 2016 Wiley Periodicals, Inc.
Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic.
Helena
H
Buchtová
Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic.
Iveta
I
Fajnerová
Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic.
Aleš
A
Stuchlík
Laboratory of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic.
Štěpán
Š
Kubík
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D000072233:Homer Scaffolding Proteins / Q000378:metabolism; D006799:Housing, Animal; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D020318:Rats, Long-Evans; D013028:Space Perception / Q000187:drug effects / Q000502:physiology
D003598:Cytoskeletal Proteins; D018691:Excitatory Amino Acid Antagonists; D000072233:Homer Scaffolding Proteins; C000606624:Homer1 protein, rat; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D016291:Dizocilpine Maleate
Arc; Homer1a; catFISH; NMDA antagonist; animal model; cognitive control; ensemble coding; hyperassociation; hypersynchrony; psychosis; schizophrenia