2000 — 2001 |
Green, John T |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
The Effects of Ethanol On the Developing Cerebellum @ Indiana University Bloomington
DESCRIPTION: (Adapted from the Investigator's Abstract) A growing body of evidence suggests that exposure to binge levels of ethanol during the brain growth spurt produces permanent deficits in both the structural and functional integrity of the cerebellum. In particular, Purkinje cells, which form the sole output of the cerebellar cortex to other brain areas, are disproportionately lost. Many of the tasks used to assess the functional impact of Purkinje cell loss are simple motor tasks, such as the rotorod and parallel bar tests. However, the precise cerebellar substrates engaged by these tasks are unknown. In contrast, a large body of evidence has been amassed on the substrates involved in a simple motor learning task, eyeblink classical conditioning. This research has shown that Purkinje cells, as well as the deep cerebellar nuclei, are critically involved in successful learning in eyeblink conditioning. The proposed research will use eyeblink conditioning procedure designed specifically to examine whether the timing of conditioned responses in adult rats is disrupted after early exposure to ethanol. Neural recording of Purkinje cells during this task will provide evidence regarding whether Purkinje cells in rats exposed to ethanol during the brain growth spurt encode the task differently from Purkinje cells in normal rats. This will allow inferences to be made regarding the functional integrity of Purkinje cells after early exposure to ethanol.
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0.948 |
2004 — 2005 |
Green, John T |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Moderate Doses of Alcohol and the Developing Cerebellum @ University of Vermont &St Agric College
DESCRIPTION (provided by applicant): The long-term objective of this research is to determine the patterns of alcohol consumption during pregnancy that results in long-term damage to the cerebellum. While it is well established that doses of alcohol that produce high blood alcohol concentrations ("binge-like exposure") over a limited portion (postnatal days 4-9) of the human third trimester-equivalent in rats can permanently damage the cerebellum, much less is known about the effects of producing lower blood alcohol concentrations over a more extended period of development. The impact on the cerebellum can be studied by combining eye blink classical conditioning, a cerebellar-dependent task that engages a well-studied and fully delineated cerebellar circuit, with counting of cerebellar cells and recording of neuronal activity in defined areas of the cerebellum. The specific aims of the proposed research are to combine these behavioral, neuroanatomical, and neurophysiological techniques to examine the impact on the adult cerebellum of acute, low dose exposure to alcohol during a longer period of the third trimester than is usually examined. Two experiments are proposed. In Experiment 1, rats will be exposed to a low dose of alcohol once per day across postnatal days 2-11. As adults they will be tested on eyeblink conditioning and cell counts of two cerebellar cell populations critical for learning, interpositus nucleus cells and Purkinje cells, will be made and compared to behavioral performance. In Experiment 2, the same neonatal treatments will be performed and, as adults, rats will be tested on eyeblink conditioning while neuronal activity from the interpositus nucleus is recorded. When completed, these results will provide important evidence regarding the extent to which moderate consumption of alcohol across an extended period of the third trimester impacts the developing cerebellum and will help to determine which alcohol consumption patterns over what time period of development damage the cerebellum. This knowledge is important for developing effective interventions and therapies for children exposed to alcohol prenatally.
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1 |
2005 — 2006 |
Green, John [⬀] |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Pp3-Hippocampal Activity During Blocking and Unblocking @ University of Vermont &St Agric College |
0.915 |
2009 — 2013 |
Green, John T Hoza, Betsy [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
A Translational Approach to Evaluating the Effects of Physical Activity On Adhd @ University of Vermont & St Agric College
DESCRIPTION (provided by applicant): Even though the exact etiological mechanisms are not yet known, there is almost universal agreement that Attention-Deficit/Hyperactivity Disorder (ADHD) is a biologically-based disorder, involving impaired self- regulation and producing cognitive, motor, social and behavioral consequences. Evidence-based treatments for ADHD focus on reducing symptoms and impairments of the disorder either through pharmacological means, the use of behavioral therapy, or both. Effects from these treatments are difficult to maintain over time (Jensen et al., 2007), and behavioral treatments are viewed as burdensome to implement by some parents and teachers. Furthermore, despite its established efficacy, pharmacological intervention is controversial in society and is viewed as unacceptable to some families. Thus, the need for additional interventions, particularly those with the potential to offer new options to families and to address ADHD symptoms at the level of brain processes, remains pressing. Towards this end, we pursue an exciting new frontier in ADHD research involving the application of an aerobic physical activity intervention for addressing the disorder, as well as its associated impairments. We approach this goal from an interdisciplinary perspective, combining expertise in neuroscience, kinesiology and both biobehavioral and clinical psychology. Importantly, our preliminary work that is based both on a rodent model of ADHD and on human work with children suggests that aerobic physical activity reduces symptoms characteristic of ADHD. Therefore, we adopt a translational strategy, including both human and animal studies, to address five specific aims: First, we examine the effect of aerobic physical activity on hyperactivity/impulsivity and inattention as well as cognitive, motor, behavioral, and social functioning in young children (ages 5-8 yrs.) and young rats (approximately 40 days old) selected for the presence of ADHD or ADHD-like symptoms, respectively. Second, we examine the minimal length of physical activity intervention required to produce an effect. Third, we examine the persistence of these effects. Fourth, through animal work, we examine the most likely neural plasticity mechanisms that may underlie the effects of physical activity on hyperactivity/impulsivity and inattention through analysis of hippocampal neurogenesis and brain derived neurotrophic factor levels.
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1 |
2013 — 2014 |
Green, John T Morielli, Anthony D |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Plasticity of Voltage Gated Ion Channels in Mammalian Learning and Memory @ University of Vermont & St Agric College
DESCRIPTION (provided by applicant): Understanding the neural mechanisms of learning and memory is of tremendous importance to human health. Alzheimer's Disease alone is estimated to affect 2.6-5.1 million Americans aged 65 years and older and to have annual costs exceeding $100 billion (NIH Fact Sheet: Alzheimer's Disease). Despite steady progress in understanding the neural basis of learning and memory, there are still major gaps in our understanding. These gaps make designing specific and effective treatments for memory disorders extremely challenging, if not impossible. This grant application addresses a major research gap in the neurobiology of mammalian learning and memory literature. Specifically, the bulk of the research on the neuronal substrates of mammalian learning and memory has focused on synaptic plasticity and regulation of ligand-gated ion channels. The proposed research will fill a major research gap by examining how regulation of voltage-gated ion channels contributes to mammalian learning and memory. In this research, we will utilize a form of mammalian learning and memory whose neural substrates in the cerebellum are well-understood (eyeblink conditioning) and study a voltage-gated ion channel whose regulation is well-understood and whose distribution in the cerebellum is highly localized (Kv1.2). Combining eyeblink conditioning and Kv1.2 gives us a model system for answering general questions about how regulation of voltage-gated ion channels contributes to mammalian learning and memory. We combine behavior, intracranial infusions, and in vivo recording to explore how and when Kv1.2 function in different regions of cerebellar cortex contributes to acquisition, expression, and extinction of eyeblink conditioning in rats and we combine behavior and biochemical assays to explore how eyeblink conditioning in rats affects cerebellar cortical Kv1.2 regulation and function.
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1 |