Early alterations in hippocampal perisomatic GABAergic synapses and network oscillations in a mouse model of Alzheimer’s disease amyloidosis

摘要: Several lines of evidence imply changes in inhibitory interneuron connectivity and subsequent alterations oscillatory network activities the pathogenesis Alzheimer’s Disease (AD). Recently, we provided for an increased immunoreactivity both postsynaptic scaffold protein gephyrin GABAA receptor γ2-subunit hippocampus young (1 3 months age), APPPS1 mice. These mice represent a well-established model cerebral amyloidosis, which is hallmark human AD. In this study, demonstrate robust increase parvalbumin accentuated projections positive (PV+) interneurons, target perisomatic regions pyramidal cells within hippocampal subregions CA1 CA3 3-month-old Colocalisation studies confirmed significant density PV+ labeled with antibodies against presynaptic (vesicular GABA transporter) marker (gephyrin) synapses cell layer CA3. As inhibition by PV+-interneurons crucial generation oscillations involved spatial processing, learning memory formation investigated impact putative enhanced on two types fast neuronal acute slices: 1. spontaneously occurring sharp wave-ripple complexes (SPW-R), 2. cholinergic γ-oscillations. Interestingly, patterns were generally preserved similar to WT However, comparison simultaneous recordings revealed that incidence amplitude SPW-Rs significantly lower vs slices, whereas power γ-oscillations was higher WT-slices indicating impaired communication between Taken together, our data GABAergic synaptic output interneurons impinging CA3, might limit coordinated cross-talk these areas mediate long-term during progression amyloidosis.