stathmin, a Gene Enriched in the Amygdala, Controls Both Learned and Innate Fear

Abstract

Little is known about the molecular mechanisms of learned and innate fear. We have identified stathmin, an inhibitor of microtubule formation, as highly expressed in the lateral nucleus (LA) of the amygdala as well as in the thalamic and cortical structures that send information to the LA about the conditioned (learned fear) and unconditioned stimuli (innate fear). Whole-cell recordings from amygdala slices that are isolated from stathmin knockout mice show deficits in spike-timing-dependent long-term potentiation (LTP). The knockout mice also exhibit decreased memory in amygdala-dependent fear conditioning and fail to recognize danger in innately aversive environments. By contrast, these mice do not show deficits in the water maze, a spatial task dependent on the hippocampus, where stathmin is not normally expressed. We therefore conclude that stathmin is required for the induction of LTP in afferent inputs to the amygdala and is essential in regulating both innate and learned fear.

Norepinephrine enables the induction of associative long-term potentiation at thalamo-amygdala synapses

“…Strong emotional memories could be established through fear conditioning, a form of associative learning, which results from assigning of predictive properties to an initially neutral conditioned stimulus (CS) after its pairing with an aversive unconditioned stimulus during behavioral training (3)(4)(5). Previous studies provide evidence for the correlative link between long-term potentiation in the CS pathways conveying auditory information to the lateral amygdala (LA) and fear learning (6)(7)(8)(9)(10). A recent work has confirmed and extended these earlier findings by showing that synaptic enhancements at the cortico-amygdala synapses could be observed in slices from conditioned animals for at least 10 days after fear conditioning (11).…”

Synaptically released zinc gates long-term potentiation in fear conditioning pathways

“…L ong-term potentiation (LTP) in afferent inputs to the amygdala is recruited during fear conditioning and used for retention of fear memory (1)(2)(3)(4)(5). A subset of glutamatergic neurons in fear conditioning pathways, including pyramidal neurons in the lateral nucleus of the amygdala (LA) where conditioned stimuli (CS) and unconditioned stimuli converge during fear learning (6)(7)(8)(9), is enriched in zinc (Zn 2ϩ ) (4).…”

Essential Role for TRPC5 in Amygdala Function and Fear-Related Behavior

“…Likewise, there was no effect of genotype on activity level, sampled immediately preceding the onset of the startle stimulus ( Figure 2B). Since TRPC5's expression pattern was consistent with its role in fear-related behaviors, we assayed conditioned freezing (learned fear) using a classical single-trial fear conditioning paradigm with a relatively strong US (2s, 0.7mA foot shock; Shumyatsky et al, 2002Shumyatsky et al, , 2005. As shown in Figure 2D, we did not observe significant differences between control and mutant mice in conditioned freezing at 24h post-training.…”

“…TRPC5 is also present in the hippocampus and dentate gyrus that project to the amygdala, and in the perirhinal cortex (PRh) that relays CS and somatosensory US information (Lanuza et al, 2004;LeDoux, 2000;Shi and Davis, 1999;Shumyatsky et al, 2005). Our findings show that responses to the CCK 2 receptor agonist, and cortico-amygdala EPSPs, mediated by Group I mGluRs, were significantly diminished in slices from TRPC5 −/− mice, while basal synaptic transmission in cortical and thalamic inputs to the LA and inputs from the LA to intercalated cells (Pare et al, 2004) was unaltered.…”

“…Regions of the auditory cortex (AuD, Au1, and AuV) that process conditioned stimulus information bound for the LA during auditory fear conditioning (Maren and Quirk, 2004), the somatosensory cortex (S1 and S2 areas) and the parietal insular cortex, regions that transmit somatosensory unconditioned stimulus (US) information to the LA, also contain TRPC5 mRNA ( Figure 1A). Finally, TRPC5 is present in the perirhinal cortex (PRh), an area involved in processing CS and somatosensory US information (Lanuza et al, 2004;LeDoux, 2000;Shi and Davis, 1999;Shumyatsky et al, 2005). Interestingly, TRPC5 mRNA was not observed in the auditory thalamus, another auditory CS area ( Figure 1B).…”