Dysfunction of cholinergic and dopaminergic systems has been implicated in memory function de cits that are core pathology and associated features of several neurological disorders. However, in order to develop more effective treatments, it is crucial to better understand how different aspects of learning and memory are modulated by these neuromodulatory systems. Using optogenetic stimulation or silencing, this thesis aims to investigate the effects of cholinergic and dopaminergic modulation on various hippocamal learning and memory processes.
To understand how these neuromodulatory systems modulate hippocampal network activity, I first examined their effects on hippocampal local field potentials in urethane-anaesthetised mice. I demonstrated that optogenetic cholinergic activation suppressed slow oscillations, shifting brain activity to a state dominated by theta and gamma oscillations. In contrast, dopaminergic activation suppressed gamma oscillations. Second, to directly probe the effects of neuromodulation on different stages of spatial learning, I acutely activated or inactivated cholinergic or dopaminergic neurons during various behavioural tasks. My findings suggested that cholinergic activation, solely during the reward phase of a long-term spatial memory task, slowed place learning, highlighting the importance of temporally-precise neuromodulation. Moreover, dopaminergic stimulation may enhance place learning of a food rewarded task, supporting a role for dopamine in spatial learning. In addition, I tested the effects of cholinergic and dopaminergic modulation on reversal learning and found that cholinergic inactivation and dopaminergic activation appear to impair this process.
Together, these findings emphasise the importance of cholinergic and dopaminergic modulation in learning and memory. They suggest that precise timing of neuromodulator action is critical for optimal learning and memory performance, and that acetylcholine and dopamine support complementary processes that allow for effective learning and adaptation to changing environments.Gulbenkian Yuval Cambridge Studentshi
