Abstract
Exposure to a stressor sensitizes or 'primes' the hypothalamic-pituitary-adrenal axis to a subsequent novel stressor. The synaptic mechanisms underlying this priming, however, are not known. We found that exposing a rat to a single stressor primed glutamate synapses in the paraventricular nucleus of the hypothalamus and allowed them to undergo a short-term potentiation (STP) following a burst of high-frequency afferent activity. This transient potentiation requires a corticotrophin-releasing hormone-dependent depression of postsynaptic NMDA receptors (NMDARs). The long-term depression of NMDAR function after stress prevented the vesicular release of an inhibitory retrograde messenger that, in control conditions, arrests STP. Following stress, STP manifested as an increase in the release probability of glutamate that was sufficient to induce multivesicular release. Our findings indicate that the priming of synapses to express STP is a synaptic correlate to stress-induced behavioral and neuroendocrine sensitization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biophysical Phenomena / drug effects
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Biophysics / methods
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Chelating Agents / pharmacology
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Corticotropin-Releasing Hormone / antagonists & inhibitors
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Corticotropin-Releasing Hormone / metabolism
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Corticotropin-Releasing Hormone / pharmacology
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Dizocilpine Maleate / pharmacology
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Drug Interactions
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Electric Stimulation / methods
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Exocytosis / drug effects
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Freezing Reaction, Cataleptic / physiology
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Glutamic Acid / metabolism*
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In Vitro Techniques
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Male
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Neurons / drug effects
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Neurons / physiology
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Paraventricular Hypothalamic Nucleus / cytology*
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Paraventricular Hypothalamic Nucleus / metabolism
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Patch-Clamp Techniques / methods
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Pyrimidines / pharmacology
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Pyrroles / pharmacology
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Quinoxalines / pharmacology
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Rats
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Rats, Sprague-Dawley
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SNARE Proteins / chemistry
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SNARE Proteins / metabolism
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SNARE Proteins / pharmacology
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Stress, Physiological / physiology*
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Synapses / drug effects
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Synapses / physiology*
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Time Factors
Substances
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CP 154526
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Chelating Agents
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Excitatory Amino Acid Antagonists
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Pyrimidines
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Pyrroles
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Quinoxalines
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SNARE Proteins
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Glutamic Acid
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Egtazic Acid
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FG 9041
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Dizocilpine Maleate
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Corticotropin-Releasing Hormone
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid