BDNF-dependent consolidation of fear memories in the perirhinal cortex

Abstract

In the recent years the perirhinal cortex (PRh) has been identified as a crucial brain area in fear learning. Since the neurotrophin brain-derived neurotrophic factor (BDNF) is an important mediator of synaptic plasticity and also crucially involved in memory consolidation of several learning paradigms, we analyzed now whether fear conditioning influences the expression of BDNF protein in the PRh. Here we observed a specific increase of BDNF protein 120 min after fear conditioning training. In order to test whether this increase of BDNF protein level is also required for the consolidation of the fear memory, we locally applied the Trk receptor inhibitor k252a into the PRh during this time window in a second series of experiments. By interfering with Trk-signaling during this critical time window, the formation of a long-term fear memory was completely blocked, indicated by a complete lack of fear potentiated startle 1 day later. In conclusion the present study further emphasizes the important role of the PRh in cued fear learning and identified BDNF as an important mediator for fear memory consolidation in the PRh.

Keywords: brain-derived neurotrophic factor; consolidation; fear learning; fear potentiated startle; perirhinal cortex.

Figure 1

BDNF protein expression in the PRh after fear conditioning training. Animals were fear conditioned, sacrificed at distinct time points after fear conditioning and the amounts of BDNF in the PRh were quantified by ELISA. We observed a strong increase in BDNF protein 120 min after fear conditioning training (solid symbols). This increase was absent in the control group (open symbols) which received the CS and US in an unpaired manner. * Represents a p-value < 0.05.

Figure 2

Histological reconstruction of coronal sections of the rat brain showing the injection sites in the PRh. BLA: basolateral amygdaloid nucleus, Ce: central amygdaloid nucleus, Cpu: caudate putamen, LA: lateral amygdaloid nucleus, PRh: perirhinal cortex, rf: rhinal fissure.

Figure 3

Blocking Trk activity 120 min after fear conditioning by local k252a application impairs fear potentiation of the acoustic startle response 24 h after fear conditioning training. (A) Mean ASR amplitude after tone-alone and light-tone trials, as well the difference scores (+SEM). (B) Relative fear potentiation of the startle amplitude by the presentation of the CS. * Represents a p-value < 0.05.