Search

The Sharp-Wave Ripple (SWR) is a signature electrophysiological phenomenon in the hippocampus, characterized by brief bursts of coordinated neural activity. SWR events are hypothesized to support learning, decision making and memory formation, but their exact role in these processes remains unclear. Since these higher level cognitive functions involve interactions between multiple brain regions, it is important to better understand how SWR events are relayed from the hippocampus to other brain structures. Hippocampal outputs to cortical regions are routed through CA1 and the subiculum, while outputs to subcortical regions are routed through the lateral septum (LS), which in turn projects to the midbrain, striatum, and other subcortical regions involved in reward processing signaled by dopamine. In this dissertation, I report results of experiments investigating how hippocampal SWRs influence single cell activity in LS and striatum, and analyze what types of information are represented by single cells that are modulated by hippocampal SWRs in the LS and striatum (Chapter 2). I also report findings from experiments in which I attempted to perform simultaneous high-temporal resolution monitoring of dopamine flux, single unit activity and LFP with a combination of fast-scan cyclic voltammetry(FSCV) and electrophysiology in the behaving rat (Chapter 3). Hungry rats repeatedly performed an acquisition-and-reversal task for food rewards on a t-maze, while chronic implants recorded SWR events in the hippocampus and single-unit spike activity in LS and striatum. During periods of motor inactivity, SWRs triggered excitatory responses from 28% (64/226) and inhibitory responses from 14% (31/226) of septal neurons. By contrast, only 4% (14/378) of striatal neurons were excited and 6% (24/378) were inhibited during SWRs. In both structures, neurons which reduced firing during SWR exhibited greater spike coherence with hippocampal theta rhythm than neurons that did not respond to SWRs. In septum, neurons that were excited by SWRs fired at late phases of the theta cycle, whereas neurons that were inhibited by SWRs fired at early phases of the theta cycle. By contrast, SWR-responsive striatal neurons did not show consistent phase preferences during the theta cycle. A subset of SWR-responsive neurons in septum (55/95) and striatum (26/38) behaved as speed cells, with firing rates that were positively or negatively modulated by the rat’s running speed. In both structures, firing rates of most SWR excited speed cells were positively modulated by running speed, whereas firing rates of most SWR-inhibited speed cells were negatively modulated by running speed.These findings are consistent with a growing body of evidence that SWRs might activate subcortical representations of motor actions in conjunction with hippocampal representations of places and states, which may be important for storing and retrieving values of state-action pairs during reinforcement learning and memory consolidation. Chapter 4 discusses implications of these results for our understanding of how SWR events contribute to learning, memory, and decision making. Further studies of SWR-evoked responses in subcortical reward circuits may build on the current findings to deepen our understanding of how SWR events contribute to cognitive functions.

Research on glutamatergic neurotransmission has focused mainly on the function of presynaptic and postsynaptic neurons, leaving astrocytes with a secondary role only to ensure successful neurotransmission. However, recent evidence indicates that astrocytes contribute actively and even regulate neuronal transmission at different levels. This review establishes a framework by comparing glutamatergic components between neurons and astrocytes to examine how astrocytes modulate or otherwise influence neuronal transmission. We have included the most recent findings about the role of astrocytes in neurotransmission, allowing us to understand the complex network of neuron-astrocyte interactions. However, despite the knowledge of synaptic modulation by astrocytes, their contribution to specific physiological and pathological conditions remains to be elucidated. A full understanding of the astrocyte’s role in neuronal processing could open fruitful new frontiers in the development of therapeutic applications.