Neural basis of time perception: The effect of optogenetic modulation of Substantia Nigra Pars Compacta on time production in mice

Perception of event durations in seconds-to-minutes range (interval timing) is observed in many vertebrate species with near identical psychophysical features. This overlap suggests a potentially well-preserved shared internal stopwatch mechanism for keeping track of time. Since there is not a sensory system specialized for time, the operation of this mechanism should heavily rely on and would be constrained by the neural processing dynamics in the brain. Many influential models of interval timing have overlooked the neural plausibility of their formulations even though they have been widely utilized as theoretical tools for the elucidation of the neural basis of time perception. A recent computational model (TopDDM) has overcome this long-standing gap by demonstrating that time perception can emerge from the neural integration of excitatory Poisson input and a proportional inhibitory Poisson input up to a constant threshold. This thesis aimed to test whether the modulation of nigrostriatal dopaminergic activity would modulate the clock speed presumably by affecting the proportionality between the excitatory and inhibitory input. Tyrosine hydroxylase-Cre (TH::Cre) mice were trained to depress the lever for a minimum amount of time to receive reward (time production). The dopaminergic neurons in the SNc region were inhibited and excited in two different groups (by viral infection and optical stimulation). Toward this end, 36 TH::Cre male mice (8–10-week-old) were taken to the experiment. These mice were divided into three groups according to their viral injections: inhibition (n = 12), excitation (n = 12), and control (n = 12). Four animals from the inhibition and excitation groups were also implanted with a microwire electrode array for electrophysiological recordings. There was a rightward shift in timed responses in the excitation group and a leftward shift in the inhibition group (between session within-group comparisons). There was no significant difference in the timing precision indices. Electrophysiological recordings confirmed increased frequency of action potentials (in mPFC) in the excitation group and reduced frequency of action potentials (in mPFC) in the inhibition group. Modeling the data in light of TopDDM suggests the role of the nigrostriatal pathway in interval timing at the level of decision-threshold setting.