Comparison of interval timing behaviour in mice following dorsal or ventral hippocampal lesions with mice having δ -opioid receptor gene deletion

Abstract

Mice with cytotoxic lesions of the dorsal hippocampus (DH) underestimated 15 s and 45 s target durations in a bi-peak procedure as evidenced by proportional leftward shifts of the peak functions that emerged during training as a result of decreases in both ‘start’ and ‘stop’ times. In contrast, mice with lesions of the ventral hippocampus (VH) displayed rightward shifts that were immediately present and were largely limited to increases in the ‘stop’ time for the 45 s target duration. Moreover, the effects of the DH lesions were congruent with the scalar property of interval timing in that the 15 s and 45 s functions superimposed when plotted on a relative timescale, whereas the effects of the VH lesions violated the scalar property. Mice with DH lesions also showed enhanced reversal learning in comparison to control and VH lesioned mice. These results are compared with the timing distortions observed in mice lacking δ -opioid receptors (Oprd1 −/− ) which were similar to mice with DH lesions. Taken together, these results suggest a balance between hippocampal–striatal interactions for interval timing and demonstrate possible functional dissociations along the septotemporal axis of the hippocampus in terms of motivation, timed response thresholds and encoding in temporal memory.

Dedicated Clock/Timing-Circuit Theories of Time Perception and Timed Performance

“…Neural oscillation is an important feature in both interval timing and working memory. In particular, the activation of working memory is associated with increased gamma oscillations (e.g., 25-100 Hz) in the frontal cortex that are entrained to the hippocampal theta-frequency range (e.g., 5-12 Hz) in multiple brain areas including the cortex, striatum, and hippocampus-all relevant to interval timing [139,144]. Recent evidence suggests that phase-amplitude coupling (PAC) of theta and gamma occurs during working memory maintenance [145][146][147]where PAC refers to the phenomenon of coupling between the amplitude of a faster oscillation and the phase of a slower oscillation.…”

Clock Speed as a Window into Dopaminergic Control of Emotion and Time Perception

“…Differential activity in the direct and indirect pathways of the basal ganglia may serve to start, stop (pause), or reset the timing process . Consequently, the SBF model has the advantage of being consistent with the known psychophysics, neuropharmacology, and neuroanatomy of interval timing while at the same time making testable predictions regarding the functioning of its components (e.g., Allman et al, 2014b;Coull et al, 2011;Hashimoto & Yotsumoto, 2015;Kononowicz, 2015;Kononowicz & van Rijn, 2014Merchant et al, 2013a;Tomasi et al, 2015;Van Rijn et al, 2011;Yin & Meck, 2014).…”

Subjective Duration as a Signature of Coding Efficiency: Emerging Links Among Stimulus Repetition, Predictive Coding, and Cortical GABA Levels

“…In this case, neural responses to pairs of stimuli separated by a fixed duration were modified by altering the weights of the excitatory connections with paired-pulse facilitation, as well as the weights of the GABAb connections to the excitatory cells of the network. As a function of repeated activation, these recurrent networks came to function as 'perceptrons' for the specific durations that were presented, thus producing circuits that display temporal generalization functions similar to those observed in psychophysical data and accounted for by the striatal beat-frequency model of interval timing (e.g., Allman & Meck, 2012;Matell & Meck, 2004, Meck et al, 1998Meck & Malapani, 2004;Van Rijn et al, in press;Yin & Meck, 2014).…”

“…1). The core-timing network consists of corticothalamic-basal ganglia circuits activated primarily by dopamine and glutamate (Cheng et al, 2006;Coull et al, 2011Coull et al, , 2013Jones & Jahanshahi, 2014;MacDonald & Meck, 2004;Matell et al, 2003;Merchant et al, 2013;Yin & Meck, 2014). The interaction between these two sets of structures supports the specific temporal judgments in a task.…”