Opposing roles of the amygdala and dorsolateral periaqueductal gray in fear-potentiated startle

Walker, David; Cassella, James V.; Lee, Young Lim; Lima, Thereza Christina Monteiro de; Davis, Michael T.

doi:10.1016/s0149-7634(96)00061-9

Cited by 99 publications

(73 citation statements)

References 68 publications

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“…Infusion of DHK in the CEA significantly increased freezing behavior when the animals were tested in a previously paired fearful context, a result that suggests intra-CEA DHK potentiates the fear response when paired with a stressful environment. Increased amygdalar activity can induce higher levels of fear that may recruit different modes of defensive responding such as increased freezing behavior (for review see Walker et al, 1997;Davis, 2006). These data are in agreement with previous reports that have shown negative or blunted startle amplitudes owing to higher doses of anxiogenic compounds in a fear-potentiated startle paradigm (Knoll et al, 2011;Reimer et al, 2012).…”

Section: Discussionsupporting

confidence: 89%

“…Furthermore, these data are consistent with our EPM data showing increased immobility (freezing behavior) after intra-CEA DHK. Increases in glutamate in specific brain regions have been shown to disrupt fear conditioning, and it has been suggested that the dense glutamatergic connections between the CEA, bed nucleus of the stria terminalis, and dorsal periaqueductal gray control the freezing response induced by increased anxiety (for review see Walker et al, 1997;Davis, 2006). The exact mechanisms through which fewer glia and resultant increases in glutamate could contribute to comorbid depression and anxiety are unknown.…”

Section: Discussionmentioning

confidence: 99%

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Blockade of the GLT-1 Transporter in the Central Nucleus of the Amygdala Induces both Anxiety and Depressive-Like Symptoms

John

Sypek

Carlezon

et al. 2015

Neuropsychopharmacol

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Depression has been associated with abnormalities in glutamatergic neurotransmission and decreased astrocyte number in limbic areas. We previously demonstrated that global and prefrontal cortical blockade of the astrocytic glutamate transporter (GLT-1) induces anhedonia and c-Fos expression in areas that regulate anxiety, including the central amygdala (CEA). Given the role of the amygdala in anxiety and the high degree of comorbidity between anxiety and depression, we hypothesized that GLT-1 blockade in the CEA would induce symptoms of anhedonia and anxiety in rats. We microinjected the GLT-1 inhibitor, dihydrokainic acid (DHK), into the CEA and examined effects on intracranial self-stimulation (ICSS) as an index of hedonic state, and on behavior in two anxiety paradigms, elevated plus maze (EPM) and fear conditioning. At lower doses, intra-CEA DHK produced modest increases in ICSS responding (T0). Higher doses resulted in complete cessation of responding for 15 min, suggesting an anhedonic or depressive-like effect. Intra-CEA DHK also increased anxiety-like behavior such that percent time in the open arms and total entries were decreased in the EPM and acquisition of freezing behavior to the tone was increased in a fear-conditioning paradigm. These effects did not appear to be explained by non-specific changes in activity, because effects on fear conditioning were assessed in a drug-free state, and a separate activity test showed no significant effects of intra-CEA DHK on locomotion. Taken together, these studies suggest that blockade of GLT-1 in the CEA is sufficient to induce both anhedonia and anxiety and therefore that a lack of glutamate uptake resulting from glial deficits may contribute to the comorbidity of depression and anxiety.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Blockade of the GLT-1 Transporter in the Central Nucleus of the Amygdala Induces both Anxiety and Depressive-Like Symptoms

John

Sypek

Carlezon

et al. 2015

Neuropsychopharmacol

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“…These functions for LepRb PAG cells are consistent with the general role for the PAG in mediating sympathetic activation (23)(24)(25) and many autonomic responses to pain (12,26) as well as the control of respiratory rate and the response to hypercapnia (19)(20)(21)(22).…”

Section: Discussionsupporting

confidence: 73%

“…The ventral PAG receives projections primarily from the spinal cord and brain stem and mediates passive coping responses, such as freezing and decreasing blood pressure (25,26). In contrast, the dorsal PAG (especially the caudal dorsal PAG) receives projections from sensory processing centers and mediates active coping responses, such as increased SNS output and flight (23)(24)(25)(26). The majority of the PAG LepRb cells lie within this caudal dorsal region of the PAG, which also contains the vast majority of noxious stimulus-activated LepRb neurons.…”

Section: Discussionmentioning

confidence: 99%

A leptin-regulated circuit controls glucose mobilization during noxious stimuli

Flak¹,

Arble²,

Pan³

et al. 2017

Journal of Clinical Investigation

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“…After conditioning, the now fearful cue alone can elicit behavioral and physiological responses similar to those initially induced by the original stressor. Studies of fear conditioning have established that the presentation of fearful cues (or fearful contexts) can enhance responses such as freezing (Blanchard and Blanchard, 1969;Phillips and LeDoux, 1992;Paylor et al, 1994 ) and can modify other responses such as fear potentiation of startle amplitude (Davis, 1992 ;Davis et al, 1995;Davis et al, 1997;Walker et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Transient fear-induced alterations in evoked release of norepinephrine and GABA in amygdala slices

2007

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Presentation of a tonal cue that previously had been associated with a fearful experience (footshock) produces alterations in arousal and sleep that occur after the fearful cue is no longer presented. To begin investigating neurochemical mechanisms that may underlie the effects of fearful cue presentation, we measured release of Depolarization-evoked release of [ 3 H]-NE from amygdalar slices of mice, which were trained to recognize a tone as a fearful cue, was suppressed at 2-3hrs after exposure of animals to the fearful cue, but recovered after 4-5 hrs. Interestingly, depolarization-evoked release of [ 14 C]-GABA was significantly increased in the amygdala, and also showed a tendency for enhancement in the hippocampus, NPO, and DRN at 2-3 hrs after cue presentation. The changes in [ 14 C]-GABA release were also transient; 4-5 hrs after cue presentation no significant differences were detected between samples derived from experimental groups which experienced fearful or neutral cues. The similar time course of fearful cue-induced changes in neurotransmitter release and changes in arousal and REM sleep suggests that alterations in amygdalar neurotransmission may be involved changes in arousal and sleep that occur after fear.

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Opposing roles of the amygdala and dorsolateral periaqueductal gray in fear-potentiated startle

Cited by 99 publications

References 68 publications

Blockade of the GLT-1 Transporter in the Central Nucleus of the Amygdala Induces both Anxiety and Depressive-Like Symptoms

Blockade of the GLT-1 Transporter in the Central Nucleus of the Amygdala Induces both Anxiety and Depressive-Like Symptoms

A leptin-regulated circuit controls glucose mobilization during noxious stimuli

Transient fear-induced alterations in evoked release of norepinephrine and GABA in amygdala slices

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