The ability to take in one’s environment, integrate relevant information, and then act appropriately is an incredibly complex feat that organisms do continuously. Disruption in the ability to think and act clearly, or cognitive dysfunction, is a debilitating aspect of neuropsychiatric diseases like schizophrenia. The prefrontal cortex and the striatum are key brain regions for functional and dysfunctional cognition, but the way that they interact to allow for cognitive processing is poorly understood. To get at these questions, I manipulated and recorded from medial frontal and striatal neurons—frontostriatal ensembles—while rats engaged in interval timing, an elementary cognitive function that engages both areas. I report four main results. First, ramping activity—a gradual, consistent change in neuronal firing rate across time—is observed throughout frontostriatal ensembles. Secondly, medial frontal areas dynamically reflect changing temporal conditions during learning and precede these same changes in striatal areas. Thirdly, interval timing and striatal ramping activity are disrupted when the medial frontal cortex is inactivated. Finally, this behavioral impairment can be reduced by optogenetic stimulation of frontostriatal terminals. My results support the view that striatal neurons integrate medial frontal activity and suggest a possible mechanism—ramping activity—through which neurons might represent the passage of time. These observations elucidate temporal processing in frontostriatal circuits and provide insight into how the medial frontal cortex exerts top-down control of cognitive processing in the striatum. My hope is that these findings will contribute to a clearer understanding of basic cognitive processing and might inform future approaches to treatments that address cognitive dysfunction.

Drosophila melanogaster is an invaluable model organism for the study of basic neuroscience. Using two previously characterized mating behaviours (Longer- and Shorter-Mating Duration), this research aims to further our knowledge of the neural circuit involved in each, and shed light on the mechanism by which four SIFamide producing neurons are involved in both. We also seek to investigate the involvement of core circadian clock genes in interval timing mechanisms. To do so, we investigated the populations of SIFamide receptor expressing neurons necessary for each behaviour and studied the contribution of circadian clock genes within the SIFamide signalling pathway. Our main experimental approach consisted of population specific knock-downs of the SIFamide receptor, the impact of which was assessed using a simple behavioural assay. This approach was complemented by rescue experiments and feminization of neurons. Finally, our investigation of the circadian clock was mediated by circadian gene knock-downs in SIFamide expressing neurons. Our results show that SIFamide signalling for each mating behaviour is mediated by segregated signalling to different, non male-specific SIFamide receptor expressing neuronal populations. We further demonstrate that SIFamide expressing neurons are not involved in the interval timing mechanism of these mating behaviours via core circadian gene contribution. This work presents preliminary results towards the investigation of a novel model of decision-making via neuronal signalling.

abstract: Temporal bisection is a common procedure for the study of interval timing in humans and non-human animals, in which participants are trained to discriminate between a “short” and a “long” interval of time. Following stable and accurate discrimination, unreinforced probe intervals between the two values are tested. In temporal bisection studies, intermediate non-reinforced probe intervals are typically arithmetically- or geometrically- spaced, yielding point of subjective equality at the arithmetic and geometric mean of the trained anchor intervals. Brown et al. (2005) suggest that judgement of the length of an interval, even when not reinforced, is influenced by its subjective length in comparison to that of other intervals. This hypothesis predicts that skewing the distribution of probe intervals shifts the psychophysical function relating interval length to the probability of reporting that interval as “long.” Data from the present temporal bisection study, using rats, suggest that there may be a within-session shift in temporal bisection responding which accounts for observed shifts in the psychophysical functions, and that this may also influence how rats categorize ambiguous intervals. / Dissertation/Thesis / Masters Thesis Psychology 2019

<p>Our perception of time is not veridical but rather is consistently modulating by changing dynamics in our environment. Anecdotal experiences suggest that emotions can be powerful modulators of time perception; nevertheless, the mechanisms underlying emotion-induced temporal distortions remain unclear. Widely accepted pacemaker-accumulator models of time perception suggest that changes in arousal and attention have unique influences on temporal judgments and contribute to emotional distortions of time perception. However, such models conflict with current views of arousal and attention and their interaction from the perspective of affective and cognitive science. The aim of this dissertation was to more clearly examine the role of arousal and attention in driving emotion-induced temporal distortions by explicitly manipulating and measuring these constructs using well-established timing procedures within the context of affective manipulations induced via classical conditioning and drug administration. Measures of physiological arousal and subjective measures of top-down attention to emotional stimuli were assessed both within and across subjects. The findings reported here suggest that current models of time perception do not adequately explain the variability in emotion-induced temporal distortions. Instead these findings provide support for a new theoretical model of emotion-induced temporal distortions proposed in the current manuscript that emphasizes both the unique and interactive influences of arousal and attention on time perception, dependent on temporal dynamics, event relationships, and individual differences. Collectively, these findings may point to plausible neurobiological mechanisms of emotion-induced temporal distortions and have important implications for our understanding of how emotions may modulate our perceptual experiences in service of adaptively responding to biologically relevant stimuli.</p> / Dissertation

abstract: Theories of interval timing have largely focused on accounting for the aggregate properties of behavior engendered by periodic reinforcement, such as sigmoidal psychophysical functions and their scalar property. Many theories of timing also stipulate that timing and motivation are inseparable processes. Such a claim is challenged by fluctuations in and out of states of schedule control, making it unclear whether motivation directly affects states related to timing. The present paper seeks to advance our understanding of timing performance by analyzing and comparing the distribution of latencies and inter-response times (IRTs) of rats in two fixed-interval (FI) schedules of food reinforcement (FI 30-s and FI 90-s), and in two levels of food deprivation. Computational modeling revealed that each component was well described by mixture probability distributions embodying two-state Markov chains. Analysis of these models revealed that only a subset of latencies are sensitive to the periodicity of reinforcement, and pre-feeding only reduces the size of this subset. The distribution of IRTs suggests that behavior in FI schedules is organized in bouts that lengthen and ramp up in frequency with proximity to reinforcement. Pre-feeding slowed down the lengthening of bouts and increased the time between bouts. When concatenated, these models adequately reproduced sigmoidal FI response functions. These findings suggest that behavior in FI fluctuates in and out of schedule control; an account of such fluctuation suggests that timing and motivation are dissociable components of FI performance. These mixture-distribution models also provide novel insights on the motivational, associative, and timing processes expressed in FI performance, which need to be accounted for by causal theories of interval timing. / Dissertation/Thesis / Masters Thesis Psychology 2015

Temporal and spatial cognition constitute basic elements of the cognitive function. Both of these competences are important for the individual's orientation and survival and there are likely to be different interactions between them. Perception of time, unlike spatial navigation and memory, is less explored. Impairments of interval timing occur in many neurodegenera- tive and neuropsychiatric disorders. According to current studies it is evident that timing is impaired even in patients with schizophrenia, but the results are still ambiguous. The aim of our work was to test the AAPA task in the time-place integration in the ani- mal model of schizophrenia. In the future, it could help to clarify the impairments of the time perception in patients with schizophrenia. In contrast to the classic AAPA task, our version included alternating of phases of light and darkness. The assumption of the experiment was that the solution of the task by rats in the dark is more dependent on the timing strategy than the solution of the task during the light, which is dependent on the spatial orientation. In the first phase of the experiment, the rats adopted both strategies - spatial (during the light phase of the session) and timing (during the dark phase). In the next phase of the experiment, we tested the animal...

Le temps est une dimension essentielle de la vie. Il est nécessaire, entre autres, pour réaliser des mouvements coordonnés, pour communiquer, mais aussi dans la prise de décisions. L’objectif principal de cette thèse était de caractériser le rôle d’un réseau amygdalo-préfronto-dorsostriatal dans la mémorisation et l’encodage du temps chez le rat. Dans un premier temps, nous avons décrit le comportement temporel du rat lors d’une tâche de suppression conditionnée (i.e. la suppression d’une réponse instrumentale d’appui sur levier par la présentation d’un son associé à un stimulus aversif), démontrant ainsi un contrôle temporel fin du comportement dans une situation Pavlovienne aversive. Dans un deuxième temps, nous avons analysé les potentiels de champs locaux (analyse fréquentielle des activités oscillatoires) de notre réseau d’intérêt au début d’un apprentissage associatif et après surentraînement dans la tâche de suppression conditionnée. En effet, le comportement temporel moteur nécessite un grand nombre de séances d’apprentissage pour devenir optimal, alors que l’apprentissage temporel est, lui, très rapide. Cette étude nous a permis de caractériser des corrélats neuronaux temporels au sein de ce réseau, que ce soit au niveau des structures individuelles ou au niveau de l’interaction entre ces structures. De plus, ces corrélats neuronaux sont modifiés selon le niveau d’entraînement des animaux. Enfin, dans une troisième étude, nous avons démontré que des ratons juvéniles (pré-sevrage), qui présentent un cortex préfrontal ainsi qu’un striatum dorsal immatures, peuvent mémoriser et différencier des intervalles de temps, ouvrant donc la question sur le rôle de ce réseau dans l’apprentissage temporel au cours du développement. / Time is an essential dimension of life. It is necessary for coordinating movement, for communication, but also for decision-making. The principal goal of this work was to characterize the role of an amygdalo-prefronto-dorsostriatal network in the memorization and encoding of time in a rat model. Firstly, we described temporal behavior in a conditioned suppression task (i.e. the suppression of an instrumental lever-pressing response for food by the presentation of a cue associated with an aversive event), therefore showing a precise temporal control in Pavlovian aversive conditioning. Secondly, we measured local field potentials in our network of interest at the beginning of associative learning and after overtraining in the conditioned suppression task. In effect, motor temporal behavior requires a large number of training sessions to become optimum, but temporal learning happens very early in training. This study allowed us to characterize, using frequency analysis of oscillatory activities, neuronal correlates of time in this network both at the level of individual structures, but also in their interactions. Interestingly, these neural correlates were modified by the level of training. Finally, we demonstrated that juvenile rats (pre-weaning), with an immature prefrontal cortex and dorsal striatum, can memorize and discriminate temporal intervals, raising questions on the role of this amygdalo-prefronto-dorsostriatal network in temporal learning during development.

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Deficits in interval timing have been described in focal brain lesions and in various neuropsychiatric disorders including Parkinson's disease (PD). The aim of this study was to explore brain areas responsible for human time perception and for the timing deficit in PD. We used a time reproduction task (TRT) which consisted of an encoding phase (during which visual stimuli of durations from 5 to 16.6 sec were presented) and a reproduction phase (during which interval durations were reproduced by a button pressing). In our first fMRI study, we used a parametric modulated analysis searching for brain areas with activity, expressed as Blood Oxygenation Level Dependent (BOLD) signal, correlated with the duration of time interval. During the encoding phase, there was a gradual deactivation of the left prefrontal cortex (PFC) and cingulate gyrus. During the reproduction phase, there was a gradual deactivation in precuneus and an accumulation of activity in the left PFC, primary motor area, right caudate and supplementary motor area (SMA). The second study aimed at supporting the role of two of these areas, SMA and precuneus in interval timing by repetitive transcranial magnetic stimulation (rTMS). Accuracy and variability of time estimates were compared before and after rTMS. Accuracy of estimates was not...

Deficits in interval timing have been described in focal brain lesions and in various neuropsychiatric disorders including Parkinson's disease (PD). The aim of this study was to explore brain areas responsible for human time perception and for the timing deficit in PD. We used a time reproduction task (TRT) which consisted of an encoding phase (during which visual stimuli of durations from 5 to 16.6 sec were presented) and a reproduction phase (during which interval durations were reproduced by a button pressing). In our first fMRI study, we used a parametric modulated analysis searching for brain areas with activity, expressed as Blood Oxygenation Level Dependent (BOLD) signal, correlated with the duration of time interval. During the encoding phase, there was a gradual deactivation of the left prefrontal cortex (PFC) and cingulate gyrus. During the reproduction phase, there was a gradual deactivation in precuneus and an accumulation of activity in the left PFC, primary motor area, right caudate and supplementary motor area (SMA). The second study aimed at supporting the role of two of these areas, SMA and precuneus in interval timing by repetitive transcranial magnetic stimulation (rTMS). Accuracy and variability of time estimates were compared before and after rTMS. Accuracy of estimates was not...