Fundamental behavioral recesses such as associative learning, rate calculation and decision-making crucially rely on estimation and reproduction of time intervals in the seconds-to-minutes range, interval timing. These processes are disrupted in Parkinson's and Huntington's diseases, Depression, Post-Traumatic Stress Disorder, Schizophrenia and Addiction. Parkinson's disease (PD) is the second most common neurodegenerative disease. PD is characterized by drastic impairments in planning and executing movement as well as cognitive deficits, some of which may be related to deficits in estimating durations. This application aims at evaluating timing deficits in mouse models of Parkinsonism in order to understand the neurobiological mechanisms involved in the perception, estimation and reproduction of durations, and in timed behavioral responses, and to rescue timing deficits through pharmacological manipulations. Our studies will help elucidate the striatal and cortical circuits involved in interval timing behavior. If successful, this project will establsh a sensitive behavioral task which could be used for early PD diagnosis and for screening for new animal models of PD, will validate this task in a mouse model of Parkinsonism using current PD medication, and will evaluate the efficiency of alternative therapeutical agents in rescuing timing deficits in mouse models when administered systemically or locally in specific brain sites. In summary, the project will enhance our understanding of neural circuits involved in cognitive and motor control deficits in movement disorders, and will help develop new treatment strategies in animal models with subsequent impact on clinical treatments.
Timekeeping is fundamental for movement, learning and goal-directed behaviors. These processes are impaired in patients with Parkinson's Disease and other movement disorders. By investigating interval timing in mouse models of Parkinsonism we aim to understand the neural circuits involved in temporal processing. The project will enhance our understanding of the role of these circuits in cognitive and motor control, and will help assessing potential treatment strategies in animal models with subsequent impact on clinical treatments.
|Buhusi, Catalin V; Reyes, Marcelo B; Gathers, Cody-Aaron et al. (2018) Inactivation of the Medial-Prefrontal Cortex Impairs Interval Timing Precision, but Not Timing Accuracy or Scalar Timing in a Peak-Interval Procedure in Rats. Front Integr Neurosci 12:20|
|Oprisan, Sorinel A; Buhusi, Mona; Buhusi, Catalin V (2018) A Population-Based Model of the Temporal Memory in the Hippocampus. Front Neurosci 12:521|
|Buhusi, Catalin V; Oprisan, Sorinel A; Buhusi, Mona (2018) Biological and Cognitive Frameworks for a Mental Timeline. Front Neurosci 12:377|
|Oprisan, Sorinel A; Aft, Tristan; Buhusi, Mona et al. (2018) Scalar timing in memory: A temporal map in the hippocampus. J Theor Biol 438:133-142|
|Buhusi, Mona; Bartlett, Mitchell J; Buhusi, Catalin V (2017) Sex differences in interval timing and attention to time in C57Bl/6J mice. Behav Brain Res 324:96-99|
|Buhusi, Mona; Brown, Colten K; Buhusi, Catalin V (2017) Impaired Latent Inhibition in GDNF-Deficient Mice Exposed to Chronic Stress. Front Behav Neurosci 11:177|
|Buhusi, Mona; Obray, Daniel; Guercio, Bret et al. (2017) Chronic mild stress impairs latent inhibition and induces region-specific neural activation in CHL1-deficient mice, a mouse model of schizophrenia. Behav Brain Res 333:1-8|
|Buhusi, Mona; Olsen, Kaitlin; Buhusi, Catalin V (2017) Increased temporal discounting after chronic stress in CHL1-deficient mice is reversed by 5-HT2C agonist Ro 60-0175. Neuroscience 357:110-118|
|Buhusi, Catalin V; Oprisan, Sorinel A; Buhusi, Mona (2016) Clocks within Clocks: Timing by Coincidence Detection. Curr Opin Behav Sci 8:207-213|
|Buhusi, Mona; Olsen, Kaitlin; Yang, Benjamin Z et al. (2016) Stress-Induced Executive Dysfunction in GDNF-Deficient Mice, A Mouse Model of Parkinsonism. Front Behav Neurosci 10:114|