Modulation of hippocampal synaptic transmission by mast cells at the hippocampal-thalamic border during early brain development

Abstract

Synaptic development is a highly structured process and can be modulated by the biogenic amine, histamine, whose dysregulation during brain development can be part of the aetiology of the neurodevelopmental disorders Tourettes syndrome and OCD. Well documented in the literature is the extensive histaminergic axonal innervation originating from neurons in tuberomammillary nucleus of the hypothalamus, however, less is known about non-neuronal sources of histamine, such as mast cells, and their potential functional importance in development. Here we set out to investigate the spatiotemporal localisation of mast cells in the developing C57Bl/6 mouse brain and the potential impact of their degranulation on developing synapses. Firstly, we find that the mouse brain contains relatively larger numbers of mast cells during the first and second postnatal week. Secondly, that in this period the highest density of mast cells is found just below the hippocampus at the hippocampal-thalamic border with lower numbers found in other brain regions. Thirdly, using the mast cell degranulator C48/80 we observe that their degranulation can facilitate synaptic transmission at the perforant pathway inputs to the ventral portion of the dentate gyrus which could not be blocked by co-application of the histamine H3 receptor antagonist thioperamide. In contrast histamine superfusion tended to decrease synaptic transmission at this pathway which was sensitive to thioperamide co-application. In conclusion, these results suggest that mast cells are present in the developing C57Bl/6 mouse brain and in particular at the hippocampal-thalamic border where upon degranulation they appear to modulate hippocampal synaptic transmission.