Neuroanatomical and Neurochemical Substrates of Timing

Abstract

We all have a sense of time. Yet, there are no sensory receptors specifically dedicated for perceiving time. It is an almost uniquely intangible sensation: we cannot see time in the way that we see color, shape, or even location. So how is time represented in the brain? We explore the neural substrates of metrical representations of time such as duration estimation (explicit timing) or temporal expectation (implicit timing). Basal ganglia (BG), supplementary motor area, cerebellum, and prefrontal cortex have all been linked to the explicit estimation of duration. However, each region may have a functionally discrete role and will be differentially implicated depending upon task context. Among these, the dorsal striatum of the BG and, more specifically, its ascending nigrostriatal dopaminergic pathway seems to be the most crucial of these regions, as shown by converging functional neuroimaging, neuropsychological, and psychopharmacological investigations in humans, as well as lesion and pharmacological studies in animals. Moreover, neuronal firing rates in both striatal and interconnected frontal areas vary as a function of duration, suggesting a neurophysiological mechanism for the representation of time in the brain, with the excitatory-inhibitory balance of interactions among distinct subtypes of striatal neuron serving to fine-tune temporal accuracy and precision.

Cannabinoid Receptor Activation Shifts Temporally Engendered Patterns of Dopamine Release

“…Previous accounts of interval timing proposed that the brain contains a neural timer that resets to zero by the occurrence of reinforcement (Gallistel and Gibbon, 2000;Gibbon, 1977) and that dopamine is critically involved in second-to-second estimation Buhusi and Meck, 2005;Coull et al, 2010;Coull et al, 2012;Matell and Meck, 2000;Meck et al, 2008;Narayanan et al, 2012;Wittmann, 2013). Consistent with this theory, we observed a decrease in subsecond dopamine concentrations throughout the interval of an FI task that resets after each reinforcement-evoked dopamine event.…”

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

“…In contrast, the changes in K* produced by the DH lesions were proportional to the target durations and scaled in a normal manner when the bi-peak functions were plotted on a relative timescale. These results strongly support a change in temporal memory resulting from hippocampal-striatal interactions such that the coincidence detection mechanism of the striatal beat-frequency model of interval timing [14,100] is biased towards shorter durations by the increased dorsal striatal activity resulting from the inhibition of DH function [12][13][14][15][101][102][103][104]. Although speculative, this proposed mechanism receives support from the proportional leftward shifts (decreases in K*) observed in Oprd1 2/2 mice which have also been shown to exhibit impaired hippocampal-dependent and facilitated striataldependent learning in a manner similar to rodents with DH lesions [36,[105][106][107][108][109][110][111].…”

The Relationship Between Auditory Processing and Restricted, Repetitive Behaviors in Adults with Autism Spectrum Disorders

“…Thus, duration discrimination appears to be a different ability to the other two. This difference between the three low-level ADTs may be due to the way in which different aspects of auditory information are differently processed at the neurological level: the intensity and frequency of auditory input are both represented in the auditory cortex, albeit in a different manner (Lockwood et al, 1999), while duration is processed outside the auditory cortex, in the basal ganglia (e.g., Coull, Nazarian, and Vidal, 2008;Jones and Jahanshahi, 2014) and they play a crucial role for both perceptual and motor timing (for reviews see Coull, Cheng and Meck 2011;Jones and Jahanshahi, 2009;Meck, Penney and Pouthas, 2008;Nayate, Bradshaw and Rinehart, 2005).…”