Corticosterone potentiation of conditioned fear in rats.
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Acoustic Stimulation↗
Biomedical subjects
J E LeDoux
Publications and source records attributed to J E LeDoux.
Response properties of single units in areas of rat auditory thalamus that project to the amygdala. I. Acoustic discharge patterns and frequency receptive fields.
Projections from the auditory thalamus to the amygdala have been implicated in the processing of the emotional significance of auditory stimuli. In order to further our understanding of the contribution of thalamoamygdala projections to auditory emotional processing, acoustic response properties of single neurons were examined in the auditory thalamus of chloral hydrate-anesthetized rats. The emphasis was on the medial division of the medial geniculate body (MGm), the suprageniculate nucleus (SG), and the posterior intralaminar nucleus (PIN), thalamic areas that receive inputs from the inferior colliculus and project to the lateral nucleus of the amygdala (AL). For comparison, recordings were also made from the specific thalamocortical relay nucleus, the ventral division of the medial geniculate body (MGv). Responses latencies were not statistically different in MGv, MGm, PIN, and SG, but were longer in the posterior thalamic region (PO). Overall, frequency tuning functions were narrower in MGv than in the other areas but many cells in MGm were as narrowly tuned as cells in MGv. There was some organization of MGv, with low frequencies represented dorsally and high frequencies ventrally. A similar but considerably weaker organization was observed in MGm. While the full range of frequencies tested (1-30 kHz) was represented in MGv, cells in MGm, PIN, and SG tended to respond best to higher frequencies (16-30 kHz). Thresholds were higher in PIN than in MGv (other areas did not differ from MGv). Nevertheless, across the various areas, the breadth of tuning was inversely related to threshold, such that more narrowly tuned cells tended to have lower thresholds. Many of the response properties observed in MGm, PIN, and SG correspond with properties found in AL neurons and thus add support to the notion that auditory responses in AL reflect thalamoamygdala transmission.
Acoustic Stimulation↗
Response properties of single units in areas of rat auditory thalamus that project to the amygdala. II. Cells receiving convergent auditory and somatosensory inputs and cells antidromically activated by amygdala stimulation.
The purpose of this study was to further our understanding of the contribution of auditory thalamoamygdala projections to conditioned emotional memories formed when auditory and noxious somatosensory stimuli are associated. Single unit activity was recorded in the acoustic thalamus of chloral hydrate-anesthetized rats in response to auditory (white noise, clicks, tones) and somatosensory (foot-shock) stimulation. The thalamic areas focused on were the medial division of the medial geniculate body (MGm), the suprageniculate nucleus (SG), and the posterior intralaminar nucleus (PIN), thalamic areas that receive inputs from both the inferior colliculus and the spinal cord and that project to the lateral nucleus of the amygdala (AL). For comparison, recordings were also made from the specific thalamocortical relay nucleus, the ventral division of the medial geniculate body (MGv), which receives projections from the inferior colliculus but not from the spinal cord. Auditory but not somatosensory responses were recorded from MGv, while both auditory and somatosensory responses were frequently found in MGm, PIN, and SG. In these areas, convergent auditory and somatosensory responses were more frequently found rostrally than caudally. Within a thalamic subregion, the acoustic response properties of the convergence cells were not different from the response properties of unimodal auditory cells. Some cells that responded to somatosensory but not auditory stimuli showed a potentiated response when tested with simultaneous presentation of auditory and somatosensory stimuli. In some studies, thalamic cells that project to the amygdala were antidromically activated by stimulation of the AL. Consistent with anatomical tracing results, antidromically activated cells were found in MGm, PIN, and SG, but not in MGv. Antidromically activated cells were more likely to respond to auditory stimuli than to somatosensory stimuli, but unimodal somatosensory and convergence cells were also found. These findings, which provide the first characterization of acoustic response properties of multimodal cells in the auditory thalamus and of cells in the auditory thalamus that project to amygdala, suggest insights into the emotional functions of the thalamoamygdala pathway.
Acoustic Stimulation↗
Emotion, memory and the brain.
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Animals↗
Emotional memory systems in the brain.
The neural mechanisms of emotion and memory have long been thought to reside side by side, if not in overlapping structures, of the limbic system. However, the limbic system concept is no longer acceptable as an account of the neural basis of memory or emotion and is being replaced with specific circuit accounts of specific emotional and memory processes. Emotional memory, a special category of memory involving the implicit (probably unconscious) learning and storage of information about the emotional significance of events, is modeled in rodent experiments using aversive classical conditioning techniques. The neural system underlying emotional memory critically involves the amygdala and structures with which it is connected. Afferent inputs from sensory processing areas of the thalamus and cortex mediate emotional learning in situations involving specific sensory cues, whereas learning about the emotional significance of more general, contextual cues involves projections to the amygdala from the hippocampal formation. Within the amygdala, the lateral nucleus (AL) is the sensory interface and the central nucleus the linkage with motor systems involved in the control of species-typical emotional behaviors and autonomic responses. Studies of cellular mechanisms in these pathways have focused on the direct relay to the lateral amygdala from the auditory thalamus. These studies show that single cells in AL respond to both conditioned stimulus and unconditioned stimulus inputs, leading to the notion that AL might be a critical site of sensory-sensory integration in emotional learning. The thalamo-amygdala pathway also exhibits long-term potentiation, a form of synaptic plasticity that might underlie the emotional learning functions of the circuit. The thalamo-amygdala pathway contains and uses the amino acid glutamate in synaptic transmission, suggesting the possibility that an amino-acid mediated form of synaptic plasticity is involved in the emotional learning functions of the pathway. We are thus well on the way to a systems level and a cellular understanding of at least one form of emotional learning and memory.
Animals↗
Extinction of emotional learning: contribution of medial prefrontal cortex.
Stimuli associated with painful or otherwise unpleasant events acquire aversive emotional properties in animals and humans. Subsequent presentation of the stimulus alone (in the absence of the unpleasant event) leads to the eventual extinction of the aversive reaction. Although the neural basis of emotional learning has been studied extensively, considerably less is known about the neural basis of emotional extinction. In the present study, we show that the medial prefrontal cortex plays an important role in the regulation of fear extinction in rats, a finding that may help elucidate the mechanisms and, possibly, the treatment of disorders of uncontrolled fear, such as anxiety, phobic, panic and posttraumatic stress disorders in humans.
Animals↗
Emotional memory: in search of systems and synapses.
The neural system underlying the conditioning of autonomic and behavioral fear responses to auditory stimuli is now understood in some detail. It involves projections through the auditory system to the medial geniculate body and from there directly to the amygdala. The lateral nucleus is the sensory interface and the central nucleus the motor interface of the amygdala. The lateral nucleus projects to the central nucleus indirectly, by way of the basolateral nucleus. Projections from the amygdala central nucleus to the midbrain central gray region mediate the behavioral responses whereas projections from the amygdala central nucleus to the lateral hypothalamus mediate the autonomic responses. Emotional memories established through such pathways bypass the neocortex and may contribute to the unconscious processing of emotion. Such memories are indelible (highly resistant to extinction). The sensory input pathway exhibits long-term synaptic potentiation and appears to utilize glutamate in synaptic transmission. An excitatory amino acid-mediated form of synaptic plasticity in the lateral amygdala may be responsible in part for emotional learning.
Animals↗
Somatosensory and auditory convergence in the lateral nucleus of the amygdala.
Previous studies have shown that the lateral nucleus of the amygdala (AL) is essential in auditory fear conditioning and that neurons in the AL respond to auditory stimuli. The goals of the present study were to determine whether neurons in the AL are also responsive to somatosensory stimuli and, if so, whether single neurons in the AL respond to both auditory and somatosensory stimulation. Single-unit activity was recorded in the AL in anesthetized rats during the presentation of acoustic (clicks) and somatosensory (footshock) stimuli. Neurons in the dorsal subdivision of the AL responded to both somatosensory and auditory stimuli, whereas neurons in the ventrolateral AL responded only to somatosensory stimuli and neurons in the ventromedial AL did not respond to either stimuli. These findings indicate that the dorsal AL is a site of auditory and somatosensory convergence and may therefore be a locus of convergence of conditioned and unconditioned stimuli in auditory fear conditioning.
Amygdala↗
Projections from the lateral nucleus to the basal nucleus of the amygdala: a light and electron microscopic PHA-L study in the rat.
A recent study, carried out in the monkey brain demonstrated a hitherto undescribed projection from the lateral to the basal nucleus of the amygdaloid complex. In the present study, we used light and electron microscopic techniques to determine whether a similar connection exists in the rat brain and to define what type(s) of synaptic contacts are produced by fibers of this projection. Injections of the lectin tracer Phaseolus vulgaris leucoagglutinin (PHA-L) were placed into several levels of the lateral nucleus and the distribution of fibers in the basal (basolateral) nucleus was evaluated. All lateral nucleus injections resulted in labeled fibers in the basal nucleus, though the density and distribution of labeled fibers depended on the position of the injection site within the lateral nucleus. In general, the heaviest labeling of the basal nucleus was observed after injections at midrostrocaudal levels of the lateral nucleus, especially when the injection was located ventrally. Fibers originating from cells labeled by these injections were observed throughout much of the rostrocaudal extent of the basal nucleus. Rostrally situated injections resulted in substantially lower levels of labeled fibers in the basal nucleus. Injections placed caudally in the lateral nucleus resulted in light to medium levels of labeled fibers in the basal nucleus; the terminal field in these cases did not extend as far rostrally as after the rostral and midlevel injections. Electron microscopic analysis of PHA-L labeled fibers revealed that they contributed synapses to the basal nucleus. The majority of PHA-L labeled terminals formed asymmetric contacts on dendritic spines or shafts; a smaller number of PHA-L labeled terminals formed symmetrical synapses.
Amygdala↗
Bilateral destruction of neocortical and perirhinal projection targets of the acoustic thalamus does not disrupt auditory fear conditioning.
The present study examined whether complete bilateral destruction of auditory cortex would interfere with auditory fear conditioning in rats. Complete destruction of auditory cortex required lesions of temporal neocortical and perirhinal periallocortical areas. Fear conditioning was assessed by measuring freezing and arterial pressure responses elicited by an acoustic stimulus after pairing with footshock. Animals with complete bilateral lesions of auditory cortex showed conditioned arterial pressure and freezing responses comparable to those of unoperated controls. In contrast, bilateral destruction of the acoustic thalamus interfered with the conditioning of both responses. These results demonstrate that the auditory cortex is not required for the conditioning of fear responses to simple acoustic stimuli and add to the growing body of evidence that fear conditioning can be mediated by subcortical (amygdaloid) projections of the acoustic thalamus.
Acoustic Stimulation↗
Brain mechanisms of emotion and emotional learning.
The amygdala appears to play an essential role in many aspects of emotional information processing and behavior. Studies over the past year have begun to clarify the anatomical organization of the amygdala and the contribution of its individual subregions to emotional functions, especially emotional learning and memory. Researchers can now point to plausible circuits involved in the transmission of sensory inputs into the amygdala, between amygdaloid subregions, and to efferent targets in cortical and subcortical regions, for specific emotional learning and memory processes.
Amygdala↗
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
The contribution of the amygdala and hippocampus to the acquisition of conditioned fear responses to a cue (a tone paired with footshock) and to context (background stimuli continuously present in the apparatus in which tone-shock pairings occurred) was examined in rats. In unoperated controls, responses to the cue conditioned faster and were more resistant to extinction than were responses to contextual stimuli. Lesions of the amygdala interfered with the conditioning of fear responses to both the cue and the context, whereas lesions of the hippocampus interfered with conditioning to the context but not to the cue. The amygdala is thus involved in the conditioning of fear responses to simple, modality-specific conditioned stimuli as well as to complex, polymodal stimuli, whereas the hippocampus is only involved in fear conditioning situations involving complex, polymodal events. These findings suggest an associative role for the amygdala and a sensory relay role for the hippocampus in fear conditioning.
Amygdala↗
Equipotentiality of thalamo-amygdala and thalamo-cortico-amygdala circuits in auditory fear conditioning.
The goal of the present study was to examine the contribution of thalamo-amygdala and thalamo-cortico-amygdala projections to fear conditioning. Lesions were used to destroy either the thalamo-cortico-amygdala projection, the thalamo-amygdala projection, or both projections, and the effects of such lesions on the acquisition of conditioned fear responses (changes in arterial pressure and freezing behavior) to a tone paired with footshock were measured. In each group of animals examined, a large lesion of the acoustic thalamus, including all nuclei of the medial geniculate body and adjacent portions of the posterior thalamus, was made on one side of the brain to block auditory transmission to the forebrain at the level of the thalamus on that side. In this way, experimental lesions could be made on the contralateral side of the brain. Thus, animals with thalamo-amygdala pathway lesions received a large lesion of the acoustic thalamus on one side. Contralaterally, only the nuclei that project to the amygdala (the medial division of the medial geniculate body, the posterior intralaminar nucleus, and the suprageniculate nucleus) were selectively destroyed, leaving much of the thalamo-cortico-amygdala projection intact. For thalamo-cortico-amygdala pathway lesions, the acoustic thalamus was destroyed on one side and temporal and perirhinal cortices were ablated contralaterally. In these animals, thalamo-amygdala projections were intact on the side of the cortical lesion. Destruction of either pathway alone had no effect on auditory fear conditioning. However, combined lesions of the two sensory pathways disrupted conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)
Amygdala↗
Overlapping projections to the amygdala and striatum from auditory processing areas of the thalamus and cortex.
The purpose of this study was to advance our understanding of the anatomical organization of sensory projections to the amygdala, and specifically to identify potential interactions within the amygdala between thalamic and cortical sensory projections of a single sensory modality. Thus, interconnections between the amygdala and acoustic processing areas of the thalamus and cortex were examined in the rat using WGA-HRP as an anterograde and a retrograde axonal tracer. Injections placed in medial aspects of the medial geniculate body (MGB) produced anterograde transport to the lateral nucleus of the amygdala and to adjacent areas of the striatum. Injections of primary auditory cortex (TE1) produced no transport to amygdala. In contrast, injections ventral to TE1 involving TE3 and perirhinal periallocortex (PRh) produced anterograde transport in the subcortical forebrain that was indistinguishable from that produced by the MGB injections. The TE3 and PRh injections also resulted in retrograde transport to primary auditory cortex and to MGB, thus confirming the involvement of these ventral cortical areas in auditory functions. Injections of the lateral nucleus of the amygdala resulted in retrograde transport back to the medial areas of MGB and to temporal cortical areas PRh, TE3, and the ventral most part of TE1. Thus, auditory processing regions of the thalamus and cortex give rise to overlapping (possibly convergent) projections to the lateral nucleus of the amygdala. These projections may allow diverse auditory signals to act on common ensembles of amygdaloid neurons and may therefore play a role in the integration of sensory messages leading to emotional reactions.
Amygdala↗
Neurons of the acoustic thalamus that project to the amygdala contain glutamate.
Injection of WGA-HRP into the lateral nucleus of the amygdala produced retrograde axonal transport to cell bodies in areas of the acoustic thalamus: the medial division of the medial geniculate body, the suprageniculate nucleus, and the posterior intralaminar nucleus. Glutamate-immunoreactive neurons were present throughout the acoustic thalamus, including the regions containing the retrogradely labeled neurons. Many of the retrogradely labeled cells were also immunoreactive for glutamate. Thus, glutamate is present in those neurons of the acoustic thalamus that project to the amygdala and may contribute to neurotransmission and synaptic plasticity in this pathway.
Amygdala↗
Ultrastructure and synaptic associations of auditory thalamo-amygdala projections in the rat.
Projections from the acoustic thalamus to the lateral nucleus of the amygdala (AL) have been implicated in the formation of emotional memories. In order to begin elucidating the cellular basis of emotional learning in this pathway, the ultrastructure and synaptic associations of acoustic thalamus efferents terminating in AL were studied using wheat-germ agglutinated horseradish peroxidase (WGA-HRP) and Phaseolus vulgaris Leucoagglutinin (Pha-L) as ultrastructural anterograde axonal markers. The tracers were injected into those areas of the thalamus (medial division of the medial geniculate body and posterior intralaminar nucleus, MGM/PIN) known both to project to AL and to receive afferents from the inferior colliculus. Terminals labeled with WGA-HRP or Pha-L in AL contained mitochondria and many small, round clear vesicles and 0-3 large, dense-core vesicles. Most labeled terminals formed asymmetric synapses on unlabeled dendrites; of these the majority were on dendritic spines. These data demonstrate that projections from the acoustic thalamus form synapses in AL and provide the first characterization of the ultrastructure and synaptic associations of sensory afferent projections to the amygdala.
Amygdala↗
Topographic organization of neurons in the acoustic thalamus that project to the amygdala.
Projections from the posterior thalamus to the amygdala have been implicated in the processing of the emotional significance of acoustic stimuli. The aim of the present studies was to determine which areas of the amygdala receive afferents from posterior thalamic structures that, in turn, receive afferents (presumably acoustic afferents) from the inferior colliculus. Projections from the posterior thalamus to the amygdala and striatum were examined in rats using anterograde and retrograde axonal transport techniques. Following injections of WGA-HRP into the posterior thalamic areas [including the medial division of the medial geniculate body, the posterior intralaminar nucleus (PIN) and the medial posterior complex (POM)], anterograde transport was seen in the lateral (AL), central (ACE), medial (AM), and basomedial (ABM) nuclei of the amygdala and in the amygdalostriatal transition area (AST) and posterior caudate putamen (CPU). Injection of WGA-HRP into each anterogradely labeled area produced retrograde transport to the posterior thalamus, but the pattern of transport varied with the site of the injection. Injections in AL and AST produced retrograde transport to neurons in the medial division of the medial geniculate body (MGM), PIN, suprageniculate nucleus (SG) and, to a lesser extent, the lateral posterior nucleus (LP). Injections of the ACE, AM, and ABM, in contrast, only labeled cells in POM. While the MGM, PIN, and SG each receive afferents from the inferior colliculus, POM does not. AL and AST, therefore, receive inputs from thalamic areas that, in turn, receive inputs from the inferior colliculus.
Amygdala↗
Unit responses evoked in the amygdala and striatum by electrical stimulation of the medial geniculate body.
Unit activity was recorded from cells and cell clusters in the amygdala and striatum in response to electrical stimulation of the medial geniculate body (MGB) in rats anesthetized with chloral hydrate. Responses were mostly excitatory and were evoked against a relatively silent background (i.e., the units seldom fired between stimuli). The shortest latency responses were recorded in the caudate putamen (CPU), lateral amygdaloid nucleus (AL), and amygdalostriatal transition area (AST). Longer latency responses were obtained from neurons in the basolateral (ABL), basomedial (ABM), and central (ACE) nuclei of the amygdala. Moreover, while responses were evoked in AL, AST, and CPU with 300-500 microA stimuli delivered once every 10 sec, more intense and higher-frequency stimuli were required to obtain responses in ABL, ABM, and ACE. These findings are consistent with anatomical tracing studies showing that AL, AST, and CPU receive direct projections from the MGB and related acoustic processing areas of the thalamus but that ACE, ABL, and ABM do not.
Amygdala↗