Relationship between Fos Production and Classical Fear Conditioning: Effects of Novelty, Latent Inhibition, and Unconditioned Stimulus Preexposure

Abstract

The relationship between FOS production in the sensory cortex and limbic system and the ability of C57BL/6N mice to acquire context- and tone-dependent freezing were investigated after fear conditioning, which was achieved by exposure of mice to context only or context and tone (10 kHz, 75 dB) as conditioned stimuli (Cs) paired with an electric footshock (0.7 mA, constant) as unconditioned stimulus (Us). The effect of preexposure to Cs or Cs paired with Us on FOS production and learning was also tested. It was demonstrated that high simultaneous FOS production in the parietal cortex, hippocampus, and amygdala paralleled the ability of mice to acquire strong freezing responses to novel Cs. After contextual preexposure (latent inhibition), FOS production could be elicited in the central amygdala only by shock and in the basolateral amygdala only by tone. Under these conditions, the ability of mice to acquire contextual freezing was almost abolished, whereas tone-dependent freezing was reduced. Lacking FOS production in the central amygdala after preexposure to context followed by shock (Us preexposure effect) paralleled the inability of mice to acquire tone-dependent freezing, although the tone elicited FOS production in the basolateral amygdala. On the basis of these findings it was concluded that synchronous Cs- and Us-induced FOS production in several defined forebrain areas was accompanied with associative learning of novel stimuli, and that a subsequent low level of FOS production might have been responsible or indicative for delayed conditioning to those stimuli.

Regulatory Mechanisms of Fear Extinction and Depression-Like Behavior

“…Contextual fear conditioning was performed as described previously (Radulovic et al, 1998a) by exposing the mice for 3 min to the context followed by a tone (30 s, 10 kHz, sinus 200 ms, 75 dB SPL) and electric shock (2 s, 0.7 mA, constant electric current) representing the unconditioned stimulus. This procedure resulted in a subceiling level of freezing that can be enhanced by repeated training trials (Li et al, 2007).…”

“…This reminder shock is not sufficient to induce fear conditioning and specifically reinstates freezing to the conditioning but not novel contexts (Fischer et al, 2004). After the end of selected experiments, tone-dependent memory tests were performed by exposing the mice to the tone for 3 min in a novel context (Radulovic et al, 1998a). These tests were performed to exclude nonspecific effects of the manipulations on freezing to a nonextinguished conditioned stimulus (tone).…”

The Activity-Regulated Cytoskeletal-Associated Protein (Arc/Arg3.1) Is Required for Memory Consolidation of Pavlovian Fear Conditioning in the Lateral Amygdala

“…Surprisingly little is known, however, about the downstream genes that underlie long-term storage of fear memories in the LA. A number of studies have examined IEG regulation in the hippocampus after either contextual (Radulovic et al, 1998;von Hertzen and Giese, 2005;Huff et al, 2006) or cued fear conditioning (Radulovic et al, 1998;Ressler et al, 2002). Other studies have examined IEG regulation in either hippocampus (Hall et al, 2001a;Strekalova et al, 2003;von Hertzen and Giese, 2005) or amygdala (Hall et al, 2001a,b) after retrieval of a fear memory.…”

A Role of Fos Expression in the CA3 Region of the Hippocampus in Spatial Memory Formation in Rats

“…The expression of c-fos is induced by a variety of stimuli (Smith et al 1992;Melia et al 1994;Duncan et al 1996) and after some forms of learning (McCabe and Horn 1994;Radulovic et al 1998;Wan et al 1999;Vann et al 2000). Accordingly, Fos expression is considered a mechanism by which brief stimuli can trigger long-term changes in gene expression and alter the structural and functional properties of nerve cells (Goelet et al 1986;Morgan and Curran 1991).…”