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Short Overview of Recent Data

Unit Recordings
CS-elicited responses in LA cells are modified after pairing with the US (Quirk et al 1995, 1997).

Conditioned plasticity also occurs in the auditory cortex (Weinberger 1995, 1998; Quirk et al 1997).

Conditioned responses in the auditory cortex occur later both within and across trials (Quirk et al 1997).

Plasticity in the auditory thalamus contributes to LA plasticity (Weinberger 1995, 1998).

Plasticity has also been observed in B during aversive conditioning (Maren et al 1991, Uwano et al 1995).

Plasticity has also been observed in CE during aversive conditioning (Pascoe & Kapp 1985).


Long-Term Potentiation
There have been a number of studies of LTP in the amygdala, mostly involving in vitro brain slices and pathways carrying information from the cortex to LA and B:

High-frequency (100 Hz) stimulation of the EC induced LTP in 80% of the AL and B cells (Chapman et al 1990).

Application of CNQX, which blocks non-NMDA excitatory amino acid receptors, reduces the monosynaptic response to EC stimulation by 85%. The remaining CNQX-insensitive response do not appear to be mediated by NMDA-type receptors, since it was not reduced by AP5, and showed none of the voltage sensitivity characteristic of NMDA responses. These data suggest that while the induction of LTP in the amygdala produced by EC stimulation is blocked by high doses of AP5, plasticity at these synapses probably does not require activation of NMDA receptors (Chapman & Bellevance 1992)

The s-EPSP could be graded by changing the stimulus intensity andsuggesting NMDA receptor-mediated s-EPSP may play an important role in epileptogenesis and synaptic plasticity in the amygdala (Gean et al 1993)

We found the induction of LTP is postsynaptic; it is dependent on postsynaptic depolarization, on the influx of Ca2+ into the postsynaptic cell and, at least in part, on the activation of NMDA receptors. Huang & Kandel 1998).

So: NMDA receptors in cortico-amygdala LTP, with some studies finding effects (Huang & Kandel 1998) and some not (Chapman & Bellevance 1992).

In vitro studies indicate that LTP in the thalamo-amygdala pathway requires postsynaptic calcium but the calcium does not enter through NMDA receptors (Weisskopf et al 1999).

Calcium entry appears through L-type voltage-gated calcium channels. These channels have also been implicated in a form of LTP that occurs in the hippocampus (Cavus & Teyler 1996).

Prior fear conditioning leads to an enhancement in synaptic responses recorded subsequently in vitro from amygdala slices (McKernan & Schinnick-Gallagher 1997).

LTP has also been found in vivo in the thalamo-amygdala pathway using recordings of extracellular field potentials (Clugnet & LeDoux 1990, Rogan & LeDoux 1995, Rogan et al 1997).

Although exploration of mechanisms are difficult in these in vivo studies, they nevertheless provide some of the strongest evidence to date in any brain system of a relation between natural learning and LTP (Barnes 1995, Eichenbaum 1995, Stevens 1998).

LTP has been found in vivo in the hippocampal-amygdala pathway, which is believed to be involved in context conditioning (Maren & Fanselow 1995).

Infusion of Drugs that Block LTP
Blockade of NMDA receptors APV prevents LTP from occurring in the amygdala. Infusion of AP5 prior to learning blocked fear conditioning, but infusion prior to testing had no effect (Miserendino et al 1990).

NMDA receptors make significant contributions to synaptic transmission in pathways that provide inputs to the amygdala: in vivo (Li et al 1995, 1996; Maren & Fanselow 1996) and in vitro (Weisskopf & LeDoux 1999).

Blockade of NMDA receptors affects both the acquisition and the expression of fear learning, which is more consistent with the transmission rather than the plasticity hypothesis(Maren et al 1996, Lee & Kim 1998).

Acquisition could be affected independently from expression however (Gewirtz & Davis 1997).


Intracellular Signaling Mechanisms
Molecular cascade similar to hippocampal LTP (See Kandel 1997) which starts with the influx of calcium during action potentials have been implicated in fear conditioning through studies of genetically altered mice (Bourtchouladze et al 1994, Mayford et al 1996, Abel et al 1997).

However, recent studies have also turned to the use of specific blockers of various signaling pathways in the brain (Bourtchouladze et al 1998, Atkins et al 1998, Josselyn et al 1998, Schafe et al 1999).

Schafe et al (1999) recently found that interference with MAP kinase, protein kinase A, and protein synthesis disrupted long-term (but not short-term) memory of both tone and contextual fear conditioning

Detractors
In spite of a wealth of data implicating the amygdala in fear conditioning, some authors have recently suggested that the amygdala is not a site of plasticity or storage during fear conditioning (e.g. Cahill & McGaugh 1998, Vazdarjanova & McGaugh 1998).

The amygdala modulates memories formed in other systems, such as declarative or explicit memories formed through hippocampal circuits or habit memories formed through striatal circuits (Packard et al 1994).

However, evidence for a role of the amygdala in modulation should not be confused with evidence against a role in plasticity (Fanselow & LeDoux 1999).

Inactivation of the amygdala during learning prevents learning from taking place (e.g. Muller et al 1997, Helmstetter & Bellgowan 1994).

If the inactivation occurs immediately after training, then there is no effect on subsequent memory, showing that the effects of pretraining treatment is on learning and not on processes that occur after learning (Wilensky et al 1999).

Plasticity within the amygdala is probably not required for learning cognitive aspects of fear, as suggest by Cahill & McGaugh (1998). This would explain why humans with amygdala damage are able to lead fairly normal lives in spite of the fact that they have certain deficits in processing danger signals.


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