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In classical conditioning, a conditioned stimulus (CS, e.g., a tone) is presented just before an unconditioned stimulus (UCS, e.g., a mild toe pinch) in repeated trials, such that the CS will eventually evoke the unconditioned response (e.g., withdrawal reflex) on its own.

Such memories of fear and discomfort are said to be held in the lateral amygdala, with a representation of the CS and its UCS (Díaz-Mataix et al, 2011).

Certain areas of the brain have particular representations of stimuli, e.g., a tone of a given frequency, as the primary auditory cortices have "tonotopic" zones in which different areas have a differential response to separate frequencies.

Since the CS/UCS pairing is more abstract than a single tone, I'm curious as to what type of representation of the CS/UCS is actually encoded within the local subnetworks amygdala. I can't imagine that, for the above example, a particular area holds a representative frequency of a tone used as a CS in tight collaboration with a "pain" signal. It might be realistic, but anatomically, that whole area would also have to reflect an exhaustive set of all of the other possible "life events" that the animal has experienced.

So, is this representation in the lateral amygdala just a placeholder to retrieve other pertinent memories stored elsewhere in cortex -- is the hippocampus a major player in keeping this sorted? If, in fact, all these pairings are just weak bindings of diverse stimuli, why is it so difficult to untangle and extinguish more complex types of fears in human patients?

Díaz-Mataix, L., Debiec, J., LeDoux, J.E. & Doyère, V. (2011). Sensory-specific associations stored in the lateral amygdala allow for selective alteration of fear memories. The Journal of Neuroscience, 31, 9538-9543.. PDF

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The lateral amygdala appears to be involved in representing fear memories after extinction (Hobin, Goosens and Maren, 2003). The extent of the lateral amygdala's involvement in representing these appears to revolve around the context of the {CS, UCS} pair. The authors state the following in their abstract:

Similarly, the majority of LA neurons exhibited context-dependent spike firing; short-latency spike firing was greater to both CSs when they were presented outside of their own extinction context. In contrast, behavioral and neuronal responses to either non-extinguished CSs or habituated auditory stimuli were not contextually modulated. Context-dependent neuronal activity in the LA may be an important mechanism for disambiguating the meaning of fear signals, thereby enabling appropriate behavioral responses to such stimuli.

You appear to be right to suspect the hippocampus' involvement. In a subsequent study by Maren and Hobin (2007) using a similar Pavlovian methodology to the previous study, the authors reported that hippocampal activity was associated with regulation of context-dependent lateral amygdaloid activity and concluded the following:

After saline infusion, rats froze more to the CS when it was presented outside of its extinction context, but froze equally in both contexts after muscimol infusion. In parallel with the behavior, lateral nucleus neurons exhibited context-dependent firing to extinguished CSs, and hippocampal inactivation disrupted this activity pattern. These data reveal a novel role for the hippocampus in regulating the context-specific firing of lateral amygdala neurons after fear memory extinction.

Finally, a context-related function of the lateral amygdala seems to provide a simple and plausible explanation for why fear extinction is far more difficult in human patients than laboratory rats: humans encounter a virtually infinite and certainly unpredictable space of possible contexts, whereas lab rats, by the nature of their unfortunate lot in life, tend to encounter relatively few and predictable contexts.

(I found it somewhat difficult to cover all the bases for your question and subquestions, so please comment if I need to expand on something.)


  • Hobin, J. A., Goosens, K. A., & Maren, S. (2003). Context-dependent neuronal activity in the lateral amygdala represents fear memories after extinction. The Journal of neuroscience, 23(23), 8410-8416.
  • Maren, S., & Hobin, J. A. (2007). Hippocampal regulation of context-dependent neuronal activity in the lateral amygdala. Learning & Memory, 14(4), 318-324. Chicago
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