| LeDoux Lab 2012 SfN Abstracts |
|---|
| Program#/Poster#: | 603.05/EEE8 |
| Title: | Temporally specific optogenetic inactivation of lateral amygdala pyramidal neurons reverses the effects of contingency degradation on fear learning. |
| Location: | Hall F-J |
| Presentation Time: | Tuesday, Oct 16, 2012, 8:00 AM - 9:00 AM |
| Authors: | *T. MADARASZ1,
E. S. BOYDEN2, J. E. LEDOUX1,3, J. P. JOHANSEN4;
1Ctr. For Neural Science, New York Univ., New York, NY; 2Media Lab, McGovern Institute, BCS, and BE Departments, MIT, Cambridge, MA; 3Nathan Kline Inst. for Psychiatric Res., Orangeburg, NY; 4RIKEN Brain Sci. Inst., Wako, Japan |
| Abstract: | Attributing appropriate
predictive power to different environmental cues is vital for the survival
of any complex organism. In classical conditioning paradigms animals learn
the association between an environmental predictive cue (conditioned stimulus
or CS) and a biologically salient aversive outcome (unconditioned stimulus
or US), and the strength of this association readily reflects the contingency
between the CS and US during training. In particular, degrading this contingency
by adding unsignaled aversive US presentations to CS-US pairings in an auditory
fear conditioning protocol attenuates the level of conditioning to the CS
(Rescorla, 1968). Thus, the predictive power of an environmental cue can
be reduced if it does not reliably signal the occurrence of the biologically
salient event. We have previously demonstrated that unpaired USs modulate the strength of auditory fear memories when presented before, during or after their formation in a time-dependent manner, suggesting that contingency degradation does not occur as a result of contextual blocking of auditory fear learning. Here we used an optogenetic approach to probe pyramidal neurons in the lateral amygdala, a site of synaptic plasticity in fear learning, as a possible anatomical locus for contingency degradation. We first infected rats bilaterally in the LA with lentivirus expressing Archaerhodopsin-T/GFP fusion protein off of a minimal CAMKIIα promoter, to target expression to LA pyramidal neurons. Four weeks after surgery and virus injection animals were given 3 CS-US pairings either followed by, or intermixed with, 12 unpaired footshocks. In both paradigms the LA was illuminated with green laser light either during the US (overlap group), or following the US with a time delay randomized around 40 seconds (offset group). We found that inactivating LA pyramidal neurons during unpaired shocks rescued levels of freezing to the tone CS compared to the offset controls, while freezing to the original training context was at similar levels for both overlap and offset animals. This demonstrates that US-evoked depolarization of LA pyramidal neurons is necessary for contingency degradation to occur, and further, that the rescue of the auditory aversive memory when these neurons are inactivated during unpaired USs is not due to a blockade of contextual fear learning. Together these results suggest that LA circuits keep track of environmental contingencies and accordingly modulate the strength of auditory aversive memories, independently of the strength of contextual fear memory. |
| Support: | NIMH R01 MH46516 |