RESUMO
Serotonergic neurons constitute one of the main systems of neuromodulators, whose diffuse projections regulate the functions of the cerebral cortex. Serotonin (5-HT) is known to play a crucial role in the differential modulation of cortical activity related to behavioral contexts. Some features of the 5-HT signaling organization suggest its possible participation as a modulator of activity-dependent synaptic changes during the critical period of the primary visual cortex (V1). Cells of the serotonergic system are among the first neurons to differentiate and operate. During postnatal development, ramifications from raphe nuclei become massively distributed in the visual cortical area, remarkably increasing the availability of 5-HT for the regulation of excitatory and inhibitory synaptic activity. A substantial amount of evidence has demonstrated that synaptic plasticity at pyramidal neurons of the superficial layers of V1 critically depends on a fine regulation of the balance between excitation and inhibition (E/I). 5-HT could therefore play an important role in controlling this balance, providing the appropriate excitability conditions that favor synaptic modifications. In order to explore this possibility, the present work used in vitro intracellular electrophysiological recording techniques to study the effects of 5-HT on the E/I balance of V1 layer 2/3 neurons, during the critical period. Serotonergic action on the E/I balance has been analyzed on spontaneous activity, evoked synaptic responses, and long-term depression (LTD). Our results pointed out that the predominant action of 5-HT implies a reduction in the E/I balance. 5-HT promoted LTD at excitatory synapses while blocking it at inhibitory synaptic sites, thus shifting the Hebbian alterations of synaptic strength towards lower levels of E/I balance.
Assuntos
Córtex Cerebral , Serotonina , Período Crítico Psicológico , Plasticidade Neuronal , Neurônios SerotoninérgicosRESUMO
The encoding of the space close to the body, named peri-personal space (PPS), is thought to play a crucial role in the unusual experiences of the self observed in schizophrenia (SCZ). However, it is unclear why SCZ patients and high schizotypal (H-SPQ) individuals present a narrower PPS and why the boundaries of the PPS are more sharply defined in patients. We hypothesise that the unusual PPS representation observed in SCZ is caused by an imbalance of excitation and inhibition (E/I) in recurrent synapses of unisensory neurons or an impairment of bottom-up and top-down connectivity between unisensory and multisensory neurons. These hypotheses were tested computationally by manipulating the effects of E/I imbalance, feedback weights and synaptic density in the network. Using simulations we explored the effects of such impairments in the PPS representation generated by the network and fitted the model to behavioural data. We found that increased excitation of sensory neurons could account for the smaller PPS observed in SCZ and H-SPQ, whereas a decrease of synaptic density caused the sharp definition of the PPS observed in SCZ. We propose a novel conceptual model of PPS representation in the SCZ spectrum that can account for alterations in self-world demarcation, failures in tactile discrimination and symptoms observed in patients.