1995 — 1997 |
Mcechron, Matthew David |
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. |
Hippocampal Cellular Mechanisms of Aging and Learning @ Northwestern University |
0.942 |
2001 |
Mcechron, Matthew David |
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. |
Aging and Ca1 Neural Modeling of Trace Fear Conditioning @ Pennsylvania State Univ Hershey Med Ctr
This pilot study will address the Neural Research Objective and will examine the neural firing pattern of CA1-hippocampal neurons is aged rats performing a learning task called trace fear conditioning. Auditory trace fear conditioning is a learning task where animal are required to associate an auditory conditioned stimulus (CS) and a fear-producing shock-unconditioned stimulus (US) that are separated by a long empty 20- second trace interval. My work has shown that association of the CS and US in trace fear conditioning in young animals is dependent on cells in the dorsal hippocampus. Pilot data suggest that a proportion of aged rats (5 of 10) are impaired in the trace fear conditioning task. My most recent neurophysiological work has demonstrated that single neurons in the CA1-hippocampus of young animals show a very robust learning-related representation of the duration of the trace interval following trace fear conditioning. Specifically, on CS-alone trails following trace fear conditioning that CA1 neurons showed a time-locked firing pattern that represented the duration of the 20-second trace interval used on previous CS-trace-US trails. /there have been only a limited number of neurophysiological studies which have examined how aging affects the neuronal encoding of learning-related information. This is partly because it has been so difficult to describe neuronal patterns of activity in the young normal brain that confidently represent learned information. However, the robust neuronal representation of the trace interval obtained during trace fear conditioning should provide an excellent tool for determining if the CA1 neurons of aged animals show altered neuronal encoding of learning-related information. Therefore, this pilot study will examine the CA1-neuronal firing pattern of young and aged rats during trace feat conditioning. Rats of three different aged groups (4,21, and 26 months) will receive two trace fear conditioning sessions where each trail consists of an auditory tone-CS and a fear-producing shock-US which are separated by a very long 20-second trace interval. Single neurons will be recorded extracellularly from Ca1 during the trace fear conditioning task to determine if neurons in aged rats encode the duration of the trace interval, and to examine how the encoding o the trace interval is related to aging-related learning deficits. This work will provide important for later studies examining how other structures in the fear conditioning circuit (e.g., amygdala, dentate, entorhinal cortex) contribute to deficient encoding of information in the CA1 of aged animals.
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0.909 |
2003 — 2004 |
Mcechron, Matthew David |
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.) |
Iron Deficiency, Hippocampal Development, and Learning @ Pennsylvania State Univ Hershey Med Ctr
DESCRIPTION (provided by applicant): The goal of this project is to identify the neural mechanisms involved in the well-established link between dietary iron deficiency (ID) and developmental impairments in learning and cognition. The hippocampus is the most important learning and memory structure in the mammalian brain. The hippocampus is critical for learning tasks that require the association of complex sets of information, and in humans it is critical for cognitive performance. Numerous studies in animals have shown that the hippocampus is more susceptible to ID during early development compared to other brain regions. An extensive list of animal and human studies has shown that ID impairs the development of learning and cognitive ability, and some of these studies suggest that these learning impairments persist well into adulthood. Together these lines of evidence strongly suggest that dietary ID alters the development of the hippocampus, and these alterations in turn significantly impact the development of children's cognitive and learning ability. Very little is known about how the functional physiology of the hippocampus is affected by ID during development. Experiment 1 in this proposal will determine if ID in postnatal developing rats impairs hippocampal synaptic responsiveness. This experiment will also determine if these physiological impairments are related to deficits in hippocampus-dependent learning. The animal learning paradigm that will be used in all of the experiments in this proposal combines trace and contextual fear conditioning, both of which have been shown to be dependent on the hippocampus. Our preliminary data demonstrate that ID in developing postnatal rats impairs learning in both of these hippocampus-dependent tasks. Our previous studies in normal adult animals have shown that single neurons in the hippocampus exhibit learning-specific encoding of the trace interval duration. Experiment 2 in this proposal will determine if ID in postnatal developing rats impairs hippocampal single neuron encoding of the trace interval duration during trace fear conditioning. Experiment 3 will determine if ID during postnatal development produces long-term impairments in hippocampal neurogenesis and hippocampus-dependent learning in young adult rats.
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0.909 |
2006 |
Mcechron, Matthew David |
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. |
Iron Nutrition/Impaired Development Motor Learning @ Pennsylvania State Univ Hershey Med Ctr
[unreadable] DESCRIPTION (provided by applicant): Iron deficiency (ID) is the most prevalent nutritional disorder in the world, and numerous reports suggest that ID during early development produces cognitive and motor impairments in children and adolescents. The present proposal will use rats to determine if perinatal ID impairs several forms of a motor learning task called eyeblink conditioning. One form of this task, called delay eyeblink conditioning, is administered by presenting an auditory conditioned stimulus (CS) and following it immediately by a periorbital unconditioned stimulus (US) which produces an eyeblink response. After repeated pairings of the CS and US, the CS will elicit a conditioned eyeblink response which precedes the US. This delay eyeblink conditioning task depends on circuits primarily through the cerebellum, a brain structure which is critical for motor coordination. If, however, a silent trace interval separates the CS and US the task is called trace eyeblink conditioning, and it depends on circuits through both the cerebellum and hippocampus. Delay and trace eyeblink conditioning can be useful tools for studying how perinatal ID affects cerebellar and hippocampal learning circuits. Our preliminary data show that rats subjected to perinatal ID are able to acquire cerebellum-dependent delay eyeblink conditioning, but they do so more slowly than control rats. These data also suggest that ID rats may show impairments in eyeblink response amplitude and timing. It is unknown if these impairments in the cerebellar task continue into adulthood after nutritional ID has been reversed. Specific Aim I will determine if perinatal ID produces irreversible impairments in cerebellum-dependent delay eyeblink conditioning which persist into adulthood after iron diets are returned to normal. A previous study from our laboratory used a much different non-motor fear conditioning task to show that perinatal ID completely prevents hippocampus-dependent fear learning, and this impairment was not reversed by a normal iron diet. Specific Aim II will determine if perinatal ID also produces complete and irreversible impairments in hippocampus-dependent motor learning (i.e., trace eyeblink conditioning). In lay terms, this proposal will help us understand the impact of iron nutrition on the development children's ability to learn fine motor skills. Moreover, eyeblink conditioning is often used in humans; therefore, this animal learning proposal could be critical for future eyeblink conditioning studies with ID in humans. [unreadable] [unreadable] [unreadable]
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0.909 |
2007 |
Mcechron, Matthew David |
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. |
Iron Nutrition and Impaired Development of Cerebellum-Dependent Motor Learning @ Pennsylvania State Univ Hershey Med Ctr
[unreadable] DESCRIPTION (provided by applicant): Iron deficiency (ID) is the most prevalent nutritional disorder in the world, and numerous reports suggest that ID during early development produces cognitive and motor impairments in children and adolescents. The present proposal will use rats to determine if perinatal ID impairs several forms of a motor learning task called eyeblink conditioning. One form of this task, called delay eyeblink conditioning, is administered by presenting an auditory conditioned stimulus (CS) and following it immediately by a periorbital unconditioned stimulus (US) which produces an eyeblink response. After repeated pairings of the CS and US, the CS will elicit a conditioned eyeblink response which precedes the US. This delay eyeblink conditioning task depends on circuits primarily through the cerebellum, a brain structure which is critical for motor coordination. If, however, a silent trace interval separates the CS and US the task is called trace eyeblink conditioning, and it depends on circuits through both the cerebellum and hippocampus. Delay and trace eyeblink conditioning can be useful tools for studying how perinatal ID affects cerebellar and hippocampal learning circuits. Our preliminary data show that rats subjected to perinatal ID are able to acquire cerebellum-dependent delay eyeblink conditioning, but they do so more slowly than control rats. These data also suggest that ID rats may show impairments in eyeblink response amplitude and timing. It is unknown if these impairments in the cerebellar task continue into adulthood after nutritional ID has been reversed. Specific Aim I will determine if perinatal ID produces irreversible impairments in cerebellum-dependent delay eyeblink conditioning which persist into adulthood after iron diets are returned to normal. A previous study from our laboratory used a much different non-motor fear conditioning task to show that perinatal ID completely prevents hippocampus-dependent fear learning, and this impairment was not reversed by a normal iron diet. Specific Aim II will determine if perinatal ID also produces complete and irreversible impairments in hippocampus-dependent motor learning (i.e., trace eyeblink conditioning). In lay terms, this proposal will help us understand the impact of iron nutrition on the development children's ability to learn fine motor skills. Moreover, eyeblink conditioning is often used in humans; therefore, this animal learning proposal could be critical for future eyeblink conditioning studies with ID in humans. [unreadable] [unreadable] [unreadable]
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0.909 |
2007 — 2011 |
Mcechron, Matthew David |
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. |
Iron Nutrition and Impaired Hippocampal Development @ Pennsylvania State Univ Hershey Med Ctr
[unreadable] DESCRIPTION (provided by applicant): Developmental iron deficiency (ID) results in impaired learning and cognition in children (e.g., Lozoff et al., 2000). This suggests that the development of one or more cognitive-learning areas in the brain may be compromised by early nutritional ID. This is alarming because ID is the most prevalent nutritional disorder in the world, and several reports show that ID during development produces cognitive impairments that are irreversible. One brain area that is severely affected by developmental ID is the hippocampus. The hippocampus is required for the association of complex sets of information, and in humans it is critical for cognitive performance. One of our recently completed studies shows that perinatal nutritional ID in rats impairs synaptic transmission in multiple subregions of the hippocampus. Another of our completed studies shows that perinatal ID in rats impairs hippocampus-dependent learning, and these learning impairments last into adulthood and are not reversed by an iron sufficient diet. These and other studies suggest that perinatal ID impairs one or more cellular processes in the hippocampus resulting in permanent learning deficits. It is not known, however, which cellular or biochemical mechanisms in the hippocampus are irreversibly impaired by perinatal ID. It is also not known if other moderate forms of perinatal ID or other genetic models of reduced iron storage capacity result in similar deficits in learning ability and cellular function in the hippocampus. Aims I and II in this proposal will address these issues. Our synaptic transmission study shows that perinatal ID impairs synaptic efficacy in multiple regions of the hippocampus. This raises the possibility that perinatal ID impairs synaptic transmission in many other learning centers outside of the hippocampus. Aim III will determine if important learning and memory centers in close proximity to the hippocampus and others far removed from the hippocampus show similar deficits in synaptic transmission. Our learning study and the work of others shows that perinatal nutritional ID impairs learning ability in animals and children. Aim IV will determine if these learning deficits can be overcome by strengthening the acquisition of information or reducing the memory retention interval. Moreover, these aims provide a comprehensive strategy for 1, identifying the neuroanatomical and cellular mechanisms permanently impacted by developmental ID; 2, determining the relationship of these mechanisms to impaired cognitive development; and 3, determining if some cognitive impairments can be reversed by manipulating the learning process. [unreadable] [unreadable] [unreadable]
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0.964 |