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Fear-Potentiated Startle with Amygdala NMDA Antagonist Infusion — WA Falls | ReplicateScience

Experiments/Fear-Potentiated Startle with Amygdala NMDA Antagonist Infusion

Source Paper

Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala

WA Falls, MJ Miserendino, M Davis

Journal of Neuroscience • 1992

Fear-Potentiated Startle with Amygdala NMDA Antagonist Infusion

behavioralNot explicitly stated in provided textNot explicitly stated in provided text

Objective: To investigate the role of NMDA receptors in the amygdala during extinction of conditioned fear responses using the fear-potentiated startle paradigm

Materials & Equipment Checklist

3 items1 from ConductScience

Gather these items before starting the experiment. Check off items as you prepare.

Equipment1

Startle apparatus

Not explicitly stated • Not provided • Not provided • Not provided

Materials2

D,L-2-amino-5-phosphonovaleric acid (AP5)

Not explicitly stated • Not applicable • Not provided • Not provided

6-cyano-7-nitroquinoxaline-2,3-dione

Not explicitly stated • Not applicable • Not provided • Not provided

1 item available from ConductScience

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Protocol Steps

1

Fear conditioning with conditioned stimulus

Animals are exposed to a conditioned stimulus paired with an unconditioned stimulus to establish fear conditioning

Not explicitly statedNot specified

Note: This establishes the baseline conditioned fear response to be extinguished

View evidence from paper

“the fear-potentiated startle paradigm was employed to begin to investigate neural mechanisms of extinction”

2

Surgical implantation of infusion cannula

Cannula implanted into the amygdala for drug infusion during extinction trials

Not explicitly statedNot specified

Note: Amygdala is the target site; interpositus nucleus of cerebellum used as control site

View evidence from paper

“infusion of the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (AP5) into the amygdala”

3

Infusion of AP5 into amygdala

NMDA antagonist AP5 infused into the amygdala in dose-dependent amounts prior to extinction trials

Not explicitly statedNot specified

Note: Dose-dependent blockade of extinction observed

View evidence from paper

“infusion of the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (AP5) into the amygdala, a limbic structure known to be important for fear conditioning, dose-dependently blocked extinction of conditioned fear”

4

Extinction trials with conditioned stimulus presentation

Conditioned stimulus presented repeatedly without unconditioned stimulus to measure extinction of fear response

Not explicitly statedNot specified

Note: Startle response measured during extinction trials

View evidence from paper

“the fear-potentiated startle paradigm was employed to begin to investigate neural mechanisms of extinction”

5

Control infusion into interpositus nucleus

AP5 infused into interpositus nucleus of cerebellum as anatomical control to verify amygdala-specific effects

Not explicitly statedNot specified

Note: Control site infusion did not block extinction

View evidence from paper

“Infusion of AP5 into the interpositus nucleus of the cerebellum, a control site, did not block extinction”

6

Control infusion of non-NMDA antagonist

6-cyano-7-nitroquinoxaline-2,3-dione infused into amygdala as pharmacological control

Not explicitly statedNot specified

Note: Non-NMDA antagonist did not block extinction, supporting NMDA-specific mechanism

View evidence from paper

“intra-amygdala infusion of a selected dose of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione did not block extinction of conditioned fear”

View Abstract

Data derived from in vitro preparations indicate that NMDA receptors play a critical role in synaptic plasticity in the CNS. More recently, in vivo pharmacological manipulations have suggested that an NMDA- dependent process may be involved in specific forms of behavioral plasticity. All of the work thus far has focused on the possible role of NMDA receptors in the acquisition of responses. However, there are many examples in the behavioral literature of learning-induced changes that involve the reduction or elimination of a previously acquired response. Experimental extinction is a primary example of the elimination of a learned response. Experimental extinction is well described in the behavioral literature, but has not received the same attention in the neurobiological literature. As a result, the neural mechanisms that underlie this important form of learning are not at all understood. In the present experiments, the fear-potentiated startle paradigm was employed to begin to investigate neural mechanisms of extinction. The results show that infusion of the NMDA antagonist D,L-2- amino-5-phosphonovaleric acid (AP5) into the amygdala, a limbic structure known to be important for fear conditioning, dose-dependently blocked extinction of conditioned fear. Control experiments showed that the blockade of extinction was neither the result of the permanent disruption of amygdaloid function nor the result of decreased sensitivity of the animals to the conditioned stimulus. Infusion of AP5 into the interpositus nucleus of the cerebellum, a control site, did not block extinction. Finally, intra-amygdala infusion of a selected dose of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione did not block extinction of conditioned fear. These results, together with a previous report from our laboratory (Miserendino et al., 1990), demonstrate the importance of the amygdala in the elaboration of conditioned fear and suggest that an NMDA-dependent process might underlie the extinction of conditioned fear.