Contributions of Dorsal/Ventral Hippocampus and Dorsolateral/Dorsomedial Striatum to Interval Timing

Humans and animals have remarkable capabilities in keeping time and using time as a guide to orient their learning and decision making. Psychophysical models of timing and time perception have been proposed for decades and have received behavioral, anatomical and pharmacological data support. However, despite numerous studies that aimed at delineating the neural underpinnings of interval timing, a complete picture of the neurobiological network of timing in the seconds-to-minutes range remains elusive. Based on classical interval timing protocols and proposing a Timing, Immersive Memory and Emotional Regulation (TIMER) test battery, the author investigates the contributions of the dorsal and ventral hippocampus as well as the dorsolateral and the dorsomedial striatum to interval timing by comparing timing performances in mice after they received cytotoxic lesions in the corresponding brain regions. On the other hand, a timing-based theoretical framework for the emergence of conscious experience that is closely related to the function of the claustrum is proposed so as to serve both biological guidance and the research and evolution of “strong” artificial intelligence. Finally, a new “Double Saturation Model of Interval Timing” that integrates the direct- and indirect- pathways of striatum is proposed to explain the set of empirical findings.

Stimulation of GABAergic neurons of the lateral septum and its effect on movement speed

The lateral septum is associated with the regulation of innate behavior, motivation, and locomotion. Its complex interconnections with cognitive and affective regions such as the hippocampus, hypothalamus, and medial septum have made it an attractive region for studying how motivation regulates behavior in context-specific settings. This GABAergic brain region’s main output is the lateral hypothalamus, which provides downstream signaling of motor commands. Even though stimulation of lateral septum projections to the hypothalamus have shown to decrease running speed in free behaving mice, characterizing movement kinematics due to LS activation has not been studied. GABAergic medium spiny neurons of the lateral septum were selectively activated through the use of optogenetic techniques in transgenic mice. Photostimulation of the lateral septum at theta frequencies caused a non-significant decrease in head and back speed. 3D motion analysis of body movement under photostimulation was quantified, revealing a slow, linear decrease of body speed as photostimulation progressed. These results support the role of lateral septum activation in movement regulation and shed light on the specific manner in which stimulation of the LS gradually decreases movement speed.