Neural Basis of Magnitude Representations and Metric Error Monitoring in Mice

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Interval timing is the ability to keep track of intervals in seconds to minutes range while counting is the ability to enumerate discrete events. The timing and counting behaviors have common variability features, suggesting that timing/counting mechanisms operate with similar processing dynamics and may even originate from a common neural locus. Humans and non-human animals account for this variability during decision-making (CCV 32, 45, 49, 62), suggesting that the endogenous uncertainty about time/counts is cognitively accessible. In support of this claim, I recently discovered that humans can monitor the direction and size of temporal, numerical, and spatial errors (e.g. CCV 5, 20, 42). This discovery (metric error monitoring - MEM) provided a new theoretical basis for the long-term (20 yrs) objective of my research program; namely the elucidation of how the brain quantifies experiences and errors in performance based on my unique combination of behavioral, computational, and neuroscientific methods. Some of my short-term objectives (5 yrs) that will lay the foundation for my long-term objective are 1) Investigation of MEM in mice: I will train mice to keep a lever depressed for a minimum duration or until a minimum number of signals is experienced. I will infer judgments about the errors in timing/counting performance based on response rates during the reward anticipation period following the release of the lever. I will also examine how metric error judgments are translated into subsequent behavioral adjustments. 2) Investigation of the neural basis of MEM in mice using optogenetics: I hypothesize that in this task responses that are earlier and later than the target magnitude are signalled by mesocortical negative and positive dopaminergic reward prediction error (dRPE), respectively and that the dRPE amplitude codes for the proximity of the performance to the target. 3) Examining the mechanistic overlap between timing and counting in mice to inform an overarching neurocomputational account of magnitude processing: I will test whether the optogenetic modulation of the activity of dopaminergic neurons in substantia nigra pars compacta biases temporal and numerical judgments similarly. By examining metric error judgments about induced biases, I will also test my model-based assertion that MEM is derived from the independent processing of magnitudes in the perceptual and motor systems (CCV 42). My NSERC program buttressed by these aims will lead to a comprehensive and overarching understanding of the quantification capacity of the brain based on causal evidence with an expected transformative impact on the conceptualization of magnitude representations and error processing in behavioral neuroscience and cognitive science. I will train HQPs in cutting-edge behavioral, computational, and neuroscience methods and their integration for studying different functions of the brain, and securing impactful research positions in and outside academia.