Poster Session 2 - B8
1,2,3Dalya Cohen, 1,2Zheng-Ping Jia, 1,3Graham Collingridge
1 Dept. of Physiology, University of Toronto; 2 Neurosciences & Mental Health, Sick Kids Hospital; 3 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital.
Alzheimer’s disease (AD) is a physiologically devastating form of dementia that has significant implications for those afflicted, as well as a high socio-economic burden. An understanding of the biological processes leading to synapse dysfunction in AD remains elusive. One promising avenue of research is to examine the dynamics of synaptic plasticity within the brain centres of learning and memory in animal models of AD. Long-term potentiation (LTP) and long-term depression (LTD) are two mechanisms underlying learning and memory at the synaptic level. Deficits in synaptic plasticity, as well as disruption of the cAMP (cyclic adenosine monophosphate) pathway have been independently proposed in AD; however it is unknown whether these are connected. The aim of this work is to examine whether synaptic defects in AD involve a neuronal signalling cascade comprising the cAMP/protein kinase A (PKA) pathway. Method: Unique modes of tetanic stimulation for induction of cAMP/PKA-dependent and -independent LTP, electrophysiological synaptic recordings in the hippocampal CA1 brain region will be used to determine whether the TgCRND8 AD model shows impairments in one or both forms of LTP. In addition, LTD experiments will provide the opportunity to identify the extent to which each memory formation pattern is altered in AD. Applying pharmacological agents that modulate the cAMP/PKA pathway in AD models may reveal more details about their role in synaptic plasticity. Examinations conducted on mouse models of AD may establish a physiologically representative picture of maladaptive LTP and LTD alterations. The work will establish whether targeting of synaptic plasticity and/or cAMP modulators holds promise for AD treatment.