1998 — 1999 |
Schafe, Glenn E |
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. |
Creb Ltp and Fear Memory
DESCRIPTION (Adapted from applicant's abstract): This proposal is aimed at defining the molecular mechanisms that underlie the consolidation of classically conditioned fear in the thalamic pathway between the medial geniculated body (MGB) and lateral amygdala (LA), a site that the neuroanatomical and pharmacological studies have suggested to be critical for the plastic changes underlying fear conditioning. In a series of behavioral and immunohistochemical experiments, we will first assess the role of both protein synthesis and the cAMP-CREB cascade in LA on the acquisition and long-term retention of conditioned fear. Subsequently, we will employ electrophysiological methods to examine the involvement of these processes in the induction and maintenance of long term potentiation (LTP) in LA following tetanic stimulation of the geniculo amygdala pathway. It is hypothesized that interference with protein synthesis or the cAMP-CREB cascade will disrupt both the long-term retention of fear memory and LTP in LA, a result that would be consistent with a large body of evidence implicating this intracellular pathway in the long-term neural and behavioral changes that accompany learning in a wide variety of species and preparations. Further investigation into the neural mechanisms of conditioned fear is expected to shed light on normal processes governing learning and memory in the mammalian brain in general, as well as provide a potential model for the study of the etiology and treatment of psychological disorders in humans, including anxiety, phobic and panic disorders in which fear is a prominent underlying symptom.
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0.97 |
2001 — 2002 |
Schafe, Glenn E |
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. |
Mapk, Ltp, and Fear Memory
Pavlovian fear conditioning has received extensive experimental attention. Much of this work has focused on defining the neuroanatomical pathways and cellular events that underlie fear. In brief, studies have suggested that fear conditioning involves sensory transmission from thalamic and cortical areas to the lateral nucleus of the amygdala (LA), where alterations in synaptic transmission are thought to encode key aspects of the learning. In contrast to the progress that has been made at the systems level in fear conditioning, relatively little is known about the molecular mechanisms that underlie fear memory consolidation. To begin to define the molecular mechanisms that underlying conditioned fear, the following proposal is aimed at evaluating the role of mitogen-activated protein (MAP) kinase in both fear memory consolidation and in long-term potentiation (LTP) in the pathway between the auditory thalamus (MGm) and the LA, which is thought to undergo plastic changes that are necessary for fear conditioning. The first set of experiments will utilize behavioral, biochemical and immunohistochemical methods to determine whether activation of MAPK in the LA is necessary for fear memory consolidation. The second set of experiments will utilize in vivo electrophysiological, biochemical, and immunohistochemical methods to assess the involvement of MAPK activation in synaptic plasticity in the MGm-LA pathway. The third set of experiments will involve a MAPK activation in the LA impairs both memory consolidation of fear conditioning-induced neural plasticity in the LA in freely behaving animals. Investigation into the molecular mechanisms of conditioned fear in animals has both the potential to shed light on normal processes governing learning and memory in general, as well as implications for the etiology and treatment of various psychological disorders. In humans, including anxiety, phobic and panic disorders, in which fear is a prominent underlying symptom.
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0.97 |
2005 — 2008 |
Schafe, Glenn |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Nitric Oxide, Synaptic Plasticity, & Fear Memory Formation in the Amygdala
The formation of memories in the brain is thought to involve the strengthening of connections between brain cells. To accomplish this strengthening, brain cells need to communicate with each other via chemical signals. The major aim of this project is to investigate the contribution of one such chemical signal: nitric oxide. The role of nitric oxide signaling will be investigated in a behavioral paradigm called fear conditioning. In this paradigm, an animal comes to learn to fear an initially emotionally neutral stimulus or object after it has been presented together with the presentation of a noxious or an aversive stimulus. Fear conditioning is known to involve alterations between brain cells in the amygdala, a specific region of the brain's temporal lobe. This project will use biochemical techniques to examine nitric oxide signaling in the amygdala during and after fear conditioning. Other experiments will employ behavioral and electrophysiological recording techniques to examine the role of nitric oxide and its targets in the formation of fear memories in the amygdala. Collectively, these experiments will add further to our understanding of the brain mechanisms underlying learning and memory in the amygdala. Further, the projects will provide an ideal training opportunity for undergraduate and graduate students in a number of different neurobiological techniques, leaving them well prepared for advanced study in the Neurosciences.
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0.915 |
2008 — 2012 |
Schafe, Glenn E |
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. |
Biochemical Mechanisms of Fear Memory Consolidation
[unreadable] DESCRIPTION (provided by applicant): A considerable amount of progress has been made in defining the neurobiological mechanisms of Pavlovian fear conditioning, both at the systems level, and also more recently at the biochemical and/or molecular levels. These findings suggest that fear conditioning involves integration of sensory information about the CS and US in lateral nucleus of the amygdala (LA), where N-Methyl-D-aspartate receptor (NMDAR)-mediated alterations in synaptic transmission are thought to encode key aspects of the learning. Most recent studies have focused their efforts on examining the role of downstream effectors of NMDAR-mediated signaling in LA cells, defining some of the key protein kinase signaling pathways that are thought to promote long-term plasticity and memory formation, in part, by engaging activators of transcription and translation in the nucleus. It has become increasingly clear, however, that the cellular mechanisms that underlie the consolidation of fear memories are not confined to alterations in LA neurons, but instead comprise a rich interaction between the LA and its afferent sensory regions that may act to promote 1) structural changes at presynaptic sites to LA neurons and 2) alterations in cell excitability throughout the wider fear network. As such, a complete understanding of the cellular and biochemical basis of fear memory consolidation will require attention to intracellular signaling cascades not only in the LA, but also in its afferent regions. The experiments outlined in each of the three Specific Aims of the present proposal are aimed at thoroughly testing this hypothesis using a combination of behavioral, biochemical, and neurophysiological recording techniques. In Specific Aim I, we will begin by further exploring the downstream nuclear substrates and transcriptional mechanisms of key protein kinase cascades in both LA and MGm/PIN, and assessing their role in the process of fear memory consolidation. In Specific Aims II and III, we will turn to the question of whether intracellular signaling cascades in the MGm/PIN that are critical for fear memory consolidation are driven by synaptic plasticity and retrograde signaling in the LA, and, in turn, whether those same thalamic signaling cascades function to promote presynaptic aspects of plasticity back in the LA. Investigation into the molecular mechanisms of conditioned fear in animals has both the potential to shed light on normal processes governing learning and memory in general, as well as implications for the etiology and treatment of various psychological disorders in humans, including anxiety, phobic and panic disorders, in which acquired fears are a prominent underlying symptom. [unreadable] [unreadable] This proposal aims to study the neural and molecular mechanisms underlying the consolidation of emotional memories in the lateral nucleus of the amygdala. Investigation into the molecular mechanisms of learned fear in animals has both the potential to shed light on normal processes governing learning and memory in general, as well as implications for the etiology and treatment of various psychological disorders in humans, including anxiety, phobic and panic disorders, in which acquired fears are a prominent underlying symptom. [unreadable] [unreadable] [unreadable]
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