From contextual fear to a dynamic view of memory systems

Abstract

The brain does not learn and remember in a unitary fashion. Rather, different circuits specialize in certain classes of problems and encode different types of information. Damage to one of these systems typically results in amnesia only for the form of memory that is the specialty of the affected region. However, the question of how the brain allocates a specific category of memory to a particular circuit has received little attention. The currently dominant view (multiple memory systems theory) assumes that such abilities are hard wired. Using fear conditioning as a paradigmatic case, I propose an alternative model in which mnemonic processing is allocated to specific circuits through a dynamic process. Potential circuits compete to form memories, with the most efficient circuits emerging as winners. However, alternate circuits compensate when these 'primary' circuits are compromised.

Figure 1. CS-US Interval

The maximum possible Conditional Rresponse (CR) is plotted for three types of conditioning with discrete trials (conditioned taste aversion in rats—CTA-Dis [8], eyeblink conditioning in rabbits—Blink-Dis [9], and fear conditioning in rats—Fear-Dis [10]) using solid lines. Dashed lines present two measures of context fear: freezing—Frz-Cont [11] and defecation—Def-Cont [11]. Because of the tremendous range of CS-US intervals between eyeblink and taste aversion learning, the abscissa plots the square root of the number of seconds between CS and US onset on a log scale. Note that the time range for discrete and contextual fear conditioning overlaps but the direction of the functions is opposite.

Figure 2

Multimodal sensory information constituting the context is integrated at the hippocampus and associated with shock in the basolateral amygdala. Descending circuitry from there generates conditional responses such as freezing and analgesia. The analgesic effects on ascending pain information from the dorsal horn constitute the error-correcting negative feedback arm of the circuit. See [- for reviews].

Figure 3

Rudy et al [42] pre-exposed intact and hippocampus-lesioned rats to a context without shock on one day. The next day the rats received a shock immediately upon placement in either the same chamber (Pre-exp) or a different chamber (Not-pre) as pre-exposure. The data measure freezing in the shocked chamber during a test given on the third day. The immediate shock deficit is illustrated by the lack of freezing in both No-pre groups. Pre-exposure increased freezing in the lesioned rats, albeit to a lesser extent than the unlesioned rats. The critical contrast showing lesioned rats profited from pre-exposure is indicated by the dark blue brackets. Based on Rudy et al [42] with permission.

Figure 4

The design and summary of results of an overtraining experiment [58] showing that rats learn context fear, albeit slowly, when the BLA is shutdown by direct infusions of the GABA agonist muscimol. Despite overtraining, rats that learn with a functional BLA needed the BLA to express fear. However, rats that learned without the BLA did not need the BLA to express fear.