IPN Seminar Series: Dana Freeman (NIH/NINDS)

Age-related changes in mitochondrial morphology and distribution compromise cholinergic synapses in basal forebrain projections to the basolateral amygdala.

Cholinergic projection neurons of the basal forebrain (BFCN) have extensively branched axonal arbors that require healthy mitochondria at terminal fields. Mitochondrial dysfunction and loss of cholinergic terminals are pathological hallmarks of Alzheimer’s disease but the relationship between these two features remains unclear. We identified mitochondria in cholinergic projections to the basolateral amygdala (BLA) using a mouse line (mito-eGFP), expressing a Cre recombinase dependent green fluorescent protein in the outer mitochondrial membrane of cholinergic neurons. We compared adolescent (1 month), adult (6 months), and aged (12,18 months) mice to determine the effect of early to late aging on mitochondrial morphology and distribution within axons. This talk will discuss the evidence that mitochondrial dysfunction is an early event in arbor destabilization in BFCN and reveal how proximity and size of pre-synaptic mitochondria impact the number of cholinergic synapses in the BLA.