By F. Mamuk. Cheyney University of Pennsylvania.
Physiol Behav 1992;51: tion of the amygdaloid central nucleus on neocortical arousal 1271–1276 cheap 25mg imipramine otc. Stress-induced hypoalgesia and defensive freez- 141 generic 25mg imipramine otc. Amygdaloid contribu- ing are attenuated by application of diazepam to the amygdala buy 25mg imipramine with amex. Antinociception emotion purchase imipramine 75 mg on-line, memory and mental dysfunction. New York: Wiley–Liss, following opioid stimulation of the basolateral amygdala is ex- 1992:229–254. Neurocomputation and learning: foundations Physiol Psychol 1980;94:313–323. Facilitation and inhibition of gastric pathology after 143. MK-801 protects condi- lesions in the amygdala in rats. Attenuation of shock-induced ulcers after lesions brane preparation. Administration of amygdaloid lesions on flight and defensive behaviors of wild thyrotropin-releasing hormone into the central nucleus of the black rats (Rattus rattus). Different types of fear- responding but not on discrimination. Psychopharmacology conditioned behaviour mediated by separate nuclei within 1987;92:491–504. Fear response and aggressive sions interfere with pavlovian negative ossasion setting. Modality-specific retrograde amnesia of campus impairs contextual retrieval of fear memory. Infusion of the non- Chapter 64: Neural Circuitry of Anxiety and Stress Disorders 949 NMDA receptor antagonist CNQX into the amygdala blocks 169. Human amygdala activa- latory systems and memory storage: role of the amygdala. Behav tion during conditioned fear acquisition and extinction: a Brain Res 1993;58:81–90. Infusion of the dopamine D1 recep- of the amygdala in neuromodulatory influences on memory tor antagonist SCH 23390 into the amygdala blocks fear expres- storage. The amygdala: neurobiological as- sion in a potentiated startle paradigm. Brain Res 1998;795: pects of emotion, memory and mental dysfunction. Functional network interac- chained conditioned stimuli in a conditioned suppression para- tions between parallel auditory pathways during pavlovian con- digm. Fear conditioning in- tioning following unilateral temporal lobectomy in humans. J duces a lasting potentiation of synaptic currents in vitro. Evidence of contextual fear loid nucleus: sensory interface of the amygdala in fear condition- conditioning following lesions of the hippocampus: a disruption ing. Decreased experi- ioral correlates of conditioned fear. J Neurosci 1988;8: mental anxiety and voluntary ethanol consumption in rats fol- 2517–2529. Interuption of projections the extinction of fear: Differential effecs of pre- or post-training from the medial geniculate mediate emotional responses condi- lesions. Amygdalar NMDA receptors are critical for frontal cortex to the acquistion and extinction of conditioned new fear learning in previously fear-conditioned rats. Lack of a temporal gradient of retro- tional learning: contribution of medial prefrontal cortex.
Although its channel at negative membrane potentials by extracellular LTP is not a unitary phenomenon cheap imipramine 25mg on line, most synapses appear magnesium order 50mg imipramine overnight delivery. As a result 25mg imipramine with visa, NMDA receptors contribute little to express a form of LTP that is identical or highly analogous to the postsynaptic response during basal synaptic activity buy imipramine 25 mg on-line. Thus, this form of LTP is the focus of the remainder ciates from its binding site within the NMDA receptor of this section. The resultant rise in intracellular calcium is a necessary and perhaps sufficient trigger for LTP. This local source of calcium within the dendritic spine ac- Triggering of LTP: A Critical Role for NMDA counts for the input specificity of LTP. Receptors and Calcium The evidence in support of this model for the initial It is well established that the triggering of LTP requires triggering of LTP is compelling. Specific NMDA receptor synaptic activation of postsynaptic N-methyl-d-aspartate antagonists have minimal effects on basal synaptic transmis- (NMDA) receptors, a subtype of ionotropic glutamate re- sion but block the generation of LTP (22,23). Preventing ceptor (see Chapter 6) and postsynaptic depolarization, the rise in calcium by loading cells with calcium chelators which is accomplished experimentally by repetitive tetanic blocks LTP (24,25), whereas directly raising intracellular stimulation of synapses or by directly depolarizing the cell calcium in the postsynaptic cell mimics LTP (25,26). How do these requirements ex- receptor activation causes a large increase in calcium level plain the properties of LTP? During basal low-frequency within dendritic spines (see 23 for references). The exact synaptic transmission, synaptically released glutamate binds properties of the calcium signal that is required to trigger to two different subtypes of ionotropic glutamate receptor, LTP are unknown, but a transient signal lasting only 1 to termed AMPA ( -amino-3-hydroxy-5-methyl-4-isoxazole 3 seconds appears to be sufficient (27). Whether additional propionic acid) and NMDA receptors, which are often, but sources of calcium, such as release from intracellular stores, not always (see later), co-localized on individual dendritic are required for the generation of LTP is unclear. The AMPA receptor has a channel that is permeable uncertain whether additional factors provide by synaptic to monovalent cations (Na and K ), and activation of activity are required. Various neurotransmitters found in AMPA receptors provides most of the inward current that the hippocampus such as acetylcholine and norepinephrine generates the excitatory synaptic response when the cell is can modulate the ability to trigger LTP, and such modula- 150 Neuropsychopharmacology: The Fifth Generation of Progress tion may be of great importance for the functional in vivo to CaMKII, whereas the tyrosine kinases Fyn and Src may roles of LTP. However, there is no compelling evidence to indirectly modulate LTP by affecting NMDA receptor suggest that any neurotransmitter other than glutamate is function (see 23 for references). Signal Transduction Mechanisms in LTP Expression Mechanisms and LTP A bewildering array of signal transduction molecules has been suggested to play a role in translating the calcium signal In the 1990s, tremendous confusion and controversy sur- that is required to trigger LTP into a long-lasting increase rounded the seemingly simple issue of whether LTP is in synaptic strength (28). However, for only a few of these caused primarily by presynaptic or postsynaptic modifica- has compelling evidence of a mandatory role in LTP been tions. The great challenge to answering this question largely presented. A major limitation of much of the work on this stemmed from the great technical difficulties inherent in topic is that investigators have not adequately distinguished examining the changes the occur at individual synapses that molecules that are key components of the signal transduc- are embedded in a complex network in which each cell tion machinery absolutely required for LTP from biochemi- receives 10,000 or more synapses. Most neurobiologists cal processes that modulate the ability to generate LTP or studying this question agree that the simplest postsynaptic play a permissive role. For example, any manipulation that change that could cause LTP would be a change in AMPA modifies the activity of NMDA receptors may affect LTP. First, it must be activated Most studies examining this issue have used electrophysi- or produced by stimuli that trigger LTP but not by stimuli ologic assays, and most of these are inconsistent with the that fail to do so. Second, inhibition of the pathway in hypothesis that the release of glutamate increases signifi- which the molecule participates should block the generation cantly during LTP (23,39). Third, activation of the pathway should lead to mitter release probability invariably influence various forms LTP. To pendent protein kinase II (CaMKII) fulfills these require- measure glutamate release more directly, two approaches ments and is a key component of the molecular machinery were used. One took advantage of the finding that glial for LTP. Inhibiting its activity pharmacologically by directly cells tightly ensheath synapses and respond to synaptically loading postsynaptic cells with CaMKII inhibitors or ge- released glutamate by activation of electrogenic transporters netic knockout of a critical CaMKII subunit blocks the that generate a current directly proportional to the amount ability to generate LTP (29–31).
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