The oxytocin receptor in sociability and cognitive flexibility: what do you learn from knockout mice models
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1
Consiglio Nazionale delle Ricerche, Institute of Neuroscience, Italy
There is a growing interest in oxytocin (OT) and vasopressin (AVP) two neuropeptides widely distributed in the central nervous system. In humans, OT and AVP participate in the regulation of emotional and social behaviours, including facial recognition and mind reading, trust, generosity, envy and gloating (Macdonald 2010 Harv Rev Psychiatry). In rodents, a number of studies have reported their activities in maternal care, pair bonding, sexual behaviour, social memory, anxiety and aggression, reward, learning and memory. In knockout mice models for OT/AVP receptors, an impairment in social recognition has been observed, strongly supporting the role of the OT/AVP system in the normal processing of socially relevant cues (Insel 2010 Neuron).
Within this line of research, we have recently characterized OT receptor null mice (Oxtr-/-) for general health, sociability, social novelty, cognitive flexibility, aggression and seizure susceptibility. We confirmed that the Oxtr-/- mice display impaired sociability and increased aggression and we reported two additional, highly relevant, phenotypic characteristics: (i) a resistance to change in a learned pattern of behavior, comparable to restricted interests and behavioral inflexibility, and (ii) an increased susceptibility to seizures. More importantly, we have shown that all these behavioral abnormalities are normalized upon the administration to adult mice of agonists that activate OT/AVP receptors (Sala 2011 Biol. Psy).
Very interestingly, the heterozygous Oxtr+/- animals, which we found to express 50% of brain OTR, show impaired sociability and a preference for social novelty like Oxtr-/- mice, but do not show impaired cognitive flexibility or increased aggression, thus indicating that the Oxtr acts as an haploinsufficient gene (Sala 2012 J Neuroendocrinol.). The expression level of this gene may thus affect specific behaviors in a dose-dependent manner: social behavior is particularly sensitive to even a partial reduction in Oxtr gene expression, whereas the emergence of aggression and cognitive inflexibility requires complete inactivation of the Oxtr gene. It is widely recognized that multiple genes and environmental factors interact with each other to produce the different psychiatric phenotypes. Our data suggest that the expression level of the Oxtr gene may be among these factors.
Finally, we have shown that Oxtr-/- hippocampal neurons display an increased ratio of glutamatergic versus GABAergic synapses (Sala 2011 Biol. Psy), an enhanced expression of excitatory, and a decreased expression of inhibitory synaptic proteins, and a parallel increased electrical activity of glutamatergic neurons. This strengthens the hypothesis of an imbalance between excitation and inhibition in specific brain circuitries as the underlying neuro-pathological substrate of neurodevelopmental and psychiatric conditions such as mental retardation, autism and schizophrenia. At present, the neural pathways selectively involved in the emergence of different psychiatric phenotypes are still largely unknown, making the Oxtr null mouse an instrumental model to investigate this crucial issue.
Keywords:
Oxytocin,
ognitive flexibility,
autism,
oxytcoin receptor,
mouse model
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
Chini
B
(2013). The oxytocin receptor in sociability and cognitive flexibility: what do you learn from knockout mice models.
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00018
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Received:
25 Jan 2013;
Published Online:
11 Apr 2013.
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Correspondence:
Dr. Bice Chini, Consiglio Nazionale delle Ricerche, Institute of Neuroscience, Milan, 20129, Italy, b.chini@in.cnr.it