Tiffany Rogers

Publications (9) View all

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  Available from: Guy Mittleman

  Article: Is autism a disease of the cerebellum? An integration of clinical and pre-clinical research

  Tiffany D Rogers, Eric Mckimm, Price E Dickson, Dan Goldowitz, Charles D Blaha, Guy Mittleman
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  ABSTRACT: Autism spectrum disorders are a group of neurodevelopmental disorders characterized by deficits in social skills and communication, stereotyped and repetitive behavior, and a range of deficits in cognitive function. While the etiology of autism is unknown, current research indicates that abnormalities of the cerebellum, now believed to be involved in cognitive function and the prefrontal cortex (PFC), are associated with autism. The current paper proposes that impaired cerebello-cortical circuitry could, at least in part, underlie autistic symptoms. The use of animal models that allow for manipulation of genetic and environmental influences are an effective means of elucidating both distal and proximal etiological factors in autism and their potential impact on cerebello-cortical circuitry. Some existing rodent models of autism, as well as some models not previously applied to the study of the disorder, display cerebellar and behavioral abnormalities that parallel those commonly seen in autistic patients. The novel findings produced from research utilizing rodent models could provide a better understanding of the neurochemical and behavioral impact of changes in cerebello-cortical circuitry in autism.
  Frontiers in Systems Neuroscience 05/2013;
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  Available from: Guy Mittleman

  Article: Reorganization of Circuits Underlying Cerebellar Modulation of Prefrontal Cortical Dopamine in Mouse Models of Autism Spectrum Disorder.

  Tiffany D Rogers, Price E Dickson, Eric McKimm, Detlef H Heck, Dan Goldowitz, Charles D Blaha, Guy Mittleman
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  ABSTRACT: Imaging, clinical, and pre-clinical studies have provided ample evidence for a cerebellar involvement in cognitive brain function including cognitive brain disorders, such as autism and schizophrenia. We previously reported that cerebellar activity modulates dopamine release in the mouse medial prefrontal cortex (mPFC) via two distinct pathways: (1) cerebellum to mPFC via dopaminergic projections from the ventral tegmental area (VTA) and (2) cerebellum to mPFC via glutamatergic projections from the mediodorsal and ventrolateral thalamus (ThN md and vl). The present study compared functional adaptations of cerebello-cortical circuitry following developmental cerebellar pathology in a mouse model of developmental loss of Purkinje cells (Lurcher) and a mouse model of fragile X syndrome (Fmr1 KO mice). Fixed potential amperometry was used to measure mPFC dopamine release in response to cerebellar electrical stimulation. Mutant mice of both strains showed an attenuation in cerebellar-evoked mPFC dopamine release compared to respective wildtype mice. This was accompanied by a functional reorganization of the VTA and thalamic pathways mediating cerebellar modulation of mPFC dopamine release. Inactivation of the VTA pathway by intra-VTA lidocaine or kynurenate infusions decreased dopamine release by 50 % in wildtype and 20-30 % in mutant mice of both strains. Intra-ThN vl infusions of either drug decreased dopamine release by 15 % in wildtype and 40 % in mutant mice of both strains, while dopamine release remained relatively unchanged following intra-ThN md drug infusions. These results indicate a shift in strength towards the thalamic vl projection, away from the VTA. Thus, cerebellar neuropathologies associated with autism spectrum disorders may cause a reduction in cerebellar modulation of mPFC dopamine release that is related to a reorganization of the mediating neuronal pathways.
  The Cerebellum 02/2013; · 3.21 Impact Factor
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  Available from: Guy Mittleman

  Article: Effects of adolescent nicotine exposure and withdrawal on intravenous cocaine self-administration during adulthood in male C57BL/6J mice.

  Price E Dickson, Mellessa M Miller, Tiffany D Rogers, Charles D Blaha, Guy Mittleman
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  ABSTRACT: Studies of adolescent drug use show (1) a pattern in which the use of tobacco precedes the use of other drugs and (2) a positive relationship between adolescent tobacco use and later drug use. These observations have led to the hypothesis that a causal relationship exists between early exposure to nicotine and the later use of hard drugs such as cocaine. Using male C57BL/6J mice, we tested the hypothesis that nicotine exposure in adolescence leads to increased intravenous self-administration (IVSA) of cocaine in adulthood. Using miniature osmotic pumps, we exposed mice and their littermate controls to nicotine (24 mg/kg/day) or vehicle, respectively, over the entire course of adolescence [postnatal days (P) 28-56]. Nicotine exposure was terminated on P56 and mice were not exposed to nicotine again during the experiment. On P73, mice were allowed to acquire cocaine IVSA (1.0 mg/kg/infusion) and a dose-response curve was generated (0.18, 0.32, 0.56, 1.0, 1.8 mg/kg/infusion). Lever pressing during extinction conditions was also evaluated. All mice rapidly learned to lever press for the combination of cocaine infusions and non-drug stimuli. Analysis of the dose-response curve revealed that adolescent nicotine-exposed mice self-administered significantly more (P < 0.05) cocaine than controls at all but the highest dose. No significant differences were observed between adolescent nicotine-exposed and control mice during the acquisition or extinction stages. These results indicate that adolescent nicotine exposure can increase cocaine IVSA in mice, which suggests the possibility of a causal link between adolescent tobacco use and later cocaine use in humans.
  Addiction Biology 09/2012; · 4.83 Impact Factor
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  Available from: Guy Mittleman

  Article: Connecting the dots of the cerebro-cerebellar role in cognitive function: neuronal pathways for cerebellar modulation of dopamine release in the prefrontal cortex.

  Tiffany D Rogers, Price E Dickson, Detlef H Heck, Dan Goldowitz, Guy Mittleman, Charles D Blaha
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  ABSTRACT: Cerebellar involvement in autism, schizophrenia, and other cognitive disorders is typically associated with prefrontal cortical pathology. However, the underlying neuronal mechanisms are largely unknown. It has previously been shown in mice that stimulation of the dentate nucleus (DN) of the cerebellum evokes dopamine (DA) release in the medial prefrontal cortex (mPFC). Here, we investigated the neuronal circuitry by which the cerebellum modulates mPFC DA release. Fixed potential amperometry was used to determine the contribution of two candidate pathways by which the cerebellum may modulate mPFC DA release. In urethane anesthetized mice, DA release evoked by DN stimulation (50 Hz) was recorded in mPFC following local anesthetic lidocaine (0.02 μg) or ionotropic glutamate receptor antagonist kynurenate (0.5 μg) infusions into the mediodorsal or ventrolateral thalamic nucleus (ThN md; ThN vl), or the ventral tegmental area (VTA). Following intra-VTA lidocaine or kynurenate infusions, DA release was decreased by ∼50%. Following intra-ThN md and ThN vl infusions of either drug, DA release was decreased by ∼35% and 15%, respectively. Reductions in DA release following lidocaine or kynurenate infusions were not significantly different indicating that neuronal cells in the VTA and ThN were activated primarily if not entirely by glutamatergic inputs. The present study suggests that neuropathological changes in the cerebellum commonly observed in autism, schizophrenia, and other cognitive disorders could result in a loss of functionality of cerebellar-mPFC circuitry that is manifested as aberrant dopaminergic activity in the mPFC. Additionally, these results specifically implicate glutamate as a modulator of mPFC dopaminergic activity.
  Synapse 06/2011; 65(11):1204-12. · 2.94 Impact Factor
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  Available from: Guy Mittleman

  Article: Genotype-dependent effects of adolescent nicotine exposure on dopamine functional dynamics in the nucleus accumbens shell in male and female mice: a potential mechanism underlying the gateway effect of nicotine.

  Price E Dickson, Tiffany D Rogers, Deranda B Lester, Mellessa M Miller, Shannon G Matta, Elissa J Chesler, Dan Goldowitz, Charles D Blaha, Guy Mittleman
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  ABSTRACT: The tendency to use cocaine is determined by genetic and environmental effects across the lifespan. One critical environmental effect is early drug exposure, which is both driven by and interacts with genetic background. The mesoaccumbens dopamine system, which is critically involved in the rewarding properties of drugs of abuse, undergoes significant development during adolescence, and thus may be at particular risk to repeated nicotine exposure during this period, thereby establishing vulnerability for subsequent adult psychostimulant use. We tested the hypotheses that adolescent nicotine exposure results in attenuation of the enhancing effects of cocaine on medial forebrain bundle (MFB) electrical stimulation-evoked dopamine release in the nucleus accumbens shell (AcbSh) in adulthood and that this effect is significantly influenced by genotype. Mice from the progenitor strains C57BL/6J and DBA/2J and those from the BXD20/TyJ and BXD86/RwwJ recombinant inbred lines were exposed to nicotine via osmotic minipumps from postnatal day (P) 28 to P56. When mice reached P70, dopamine functional dynamics in AcbSh was evaluated by means of in vivo fixed potential amperometry in combination with electrical stimulation of mesoaccumbens dopaminergic axons in the MFB. Adolescent exposure to nicotine in all strains dose-dependently reduced the ability of a fixed-dose challenge injection of cocaine (10 mg/kg, i.p.) to enhance MFB electrical stimulation-evoked dopamine release in AcbSh in adults. The magnitude of this effect was genotype-dependent. These results suggest a genotype-dependent mechanism by which nicotine exposure during adolescence causes persistent changes in the sensitivity to "hard" stimulants such as cocaine.
  Psychopharmacologia 01/2011; 215(4):631-42. · 4.08 Impact Factor