Glutamatergic transmission is enhanced in the amygdala in experimental autoimmune encephalomyelitis

Abstract

Multiple sclerosis (MS) is often associated with co-morbidities like neuropsychiatric and cognitive impairments, affecting around 50% of the patients. We investigated these abnormalities in an animal model of MS, called experimental autoimmune encephalomyelitis (EAE) during the early onset of the disease. We have shown that at this presymptomatic stage, the EAE mice show emotional and cognitive deficits in absence of motor deficit. Whole-cell recording was carried out in the principal neurons of basolateral amygdala (BLA) to investigate the neuronal correlates of these behaviour changes. Investigation into glutamatergic synaptic transmission revealed increased frequency of the mini-excitatory postsynaptic currents (mEPSC) without any changes in amplitude compared to the controls; this was indicative of increased glutamate release. This was associated an increase in the synaptic spines in the principal neurons of the BLA. AMPA: NMDA ratio was increased in EAE mice and there was an alteration in the AMPA receptor subunit composition, with an increase in GluA2 subunit. In conclusion, emotional and cognitive deficits observed in EAE (and possibly MS) were associated with an increased dendrite spines, enhanced glutamatergic transmission and changes in AMPA receptor composition in the BLA.