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Protein-phosphatase 1 and its role in long-term depression in the amygdala


Mirante, O M. Protein-phosphatase 1 and its role in long-term depression in the amygdala. 2015, ETH Zürich, Faculty of Science.

Abstract

The brain observes, detects, learns, and remembers signals coming from our external environment. In particular, it senses danger, and once detected, the related sensory signal, be it auditory, visual or somatosensory, triggers synaptic plasticity, enabling the brain to learn and remember the event. During Pavlovian fear conditioning, animals learn to associate a negative stimulus, such as a mild foot-shock, witha neutral stimulus, like a novel sound or context. This association leads to long-lasting changes in the animals’ behavior upon re-exposure to the neutral stimuli that, in rodent, is expressed by a “freezing” fear posture. Fortunately, these fear memories, in rodent and human, extinguish with repeated exposure to the neutral stimuli in absence of the negative stimulus. If fear extinction were impaired, however, one would live every day in an anxious state of exaggerated fear. Humans with post-traumatic stress disorder suffer from a persistent fear memory that is resistant to extinction. Although therapies based on extinction already exist, their efficiency is low and the majority of patients experience relapse.
This thesis proposes that a detailed investigation of the molecular mechanisms underlying the synaptic plasticity of fear extinction will enable better treatment for anxiety disorders, and uses electrophysiology to step modestly in that direction.Fear memory formation and extinction occur principally in the amygdala, a brain area localized within the temporal lobe. The amygdala receives sensory stimuli primarily from the thalamus and cortex and long-term potentiation of thalamo-and cortico-amygdalar synaptic transmission is believed to underlie fear memory formation. In contrast, fear extinction is thought to involve long-termdepression of these circuits. My doctorate focused on understanding the molecular pathways underlying long-term depression of thalamo-and cortico-amygdalar projections. I found that thalamic and cortical inputs carry distinctmolecular pathways, such as distinct receptors localized at differentsites of long-term depression induction.

The brain observes, detects, learns, and remembers signals coming from our external environment. In particular, it senses danger, and once detected, the related sensory signal, be it auditory, visual or somatosensory, triggers synaptic plasticity, enabling the brain to learn and remember the event. During Pavlovian fear conditioning, animals learn to associate a negative stimulus, such as a mild foot-shock, witha neutral stimulus, like a novel sound or context. This association leads to long-lasting changes in the animals’ behavior upon re-exposure to the neutral stimuli that, in rodent, is expressed by a “freezing” fear posture. Fortunately, these fear memories, in rodent and human, extinguish with repeated exposure to the neutral stimuli in absence of the negative stimulus. If fear extinction were impaired, however, one would live every day in an anxious state of exaggerated fear. Humans with post-traumatic stress disorder suffer from a persistent fear memory that is resistant to extinction. Although therapies based on extinction already exist, their efficiency is low and the majority of patients experience relapse.
This thesis proposes that a detailed investigation of the molecular mechanisms underlying the synaptic plasticity of fear extinction will enable better treatment for anxiety disorders, and uses electrophysiology to step modestly in that direction.Fear memory formation and extinction occur principally in the amygdala, a brain area localized within the temporal lobe. The amygdala receives sensory stimuli primarily from the thalamus and cortex and long-term potentiation of thalamo-and cortico-amygdalar synaptic transmission is believed to underlie fear memory formation. In contrast, fear extinction is thought to involve long-termdepression of these circuits. My doctorate focused on understanding the molecular pathways underlying long-term depression of thalamo-and cortico-amygdalar projections. I found that thalamic and cortical inputs carry distinctmolecular pathways, such as distinct receptors localized at differentsites of long-term depression induction.

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Additional indexing

Item Type:Dissertation
Referees:Mansuy I M, Gerber U, Stoop R
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2015
Deposited On:29 Feb 2016 09:53
Last Modified:12 Jul 2016 08:16
Permanent URL: https://doi.org/10.5167/uzh-123100

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