Differential regional expression of brain-derived neurotrophic factor following olfactory fear learning

Abstract

We examined brain-derived neurotrophic factor (BDNF) mRNA expression across the olfactory system following fear conditioning. Mice received 10 pairings of odor with footshock or equivalent unpaired odors and shocks. We found increased BDNF mRNA in animals receiving paired footshocks in the multiple regions examined including the posterior piriform cortex (PPC) and basolateral amygdala (BLA). This was in contrast to the unpaired and odor-alone treatments, where BDNF mRNA was increased in the olfactory bulb (OB) and anterior piriform cortex (APC) only, but not the higher olfactory areas. We propose that odor exposure increases expression of BDNF in the OB and APC while the PPC and BLA increase BDNF mRNA only when associative learning occurs.Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that has been shown to play a role in learning and memory (Tyler et al. 2002;Rattiner et al. 2005). Besides its neurotrophic activity, BDNF, working through its primary receptor TrkB, is involved in a number of downstream effects related to learning including long-term synaptic plasticity (Lohof et al. 1993;Korte et al. 1995), morphological changes in dendritic spines (Tyler and Pozzo-Miller 2003;Rex et al. 2007), gene transcription via CREB (Minichiello et al. 2002), and the recruitment of PSD-95 to the synapse (Yoshii and Constantine-Paton 2007).In the hippocampus, BDNF mRNA increases with hippocampal-dependent tasks such as the Morris Water Maze (Falkenberg et al. 1992) and contextual learning (Hall et al. 2000;Mizuno et al. 2000). Locally blocking the action of BDNF prevents learning in hippocampal-dependent tasks as shown by infusion of antisense BDNF oligonucleotides (Mizuno et al. 2000) and by regional knock-out of BDNF (Heldt et al. 2007). In the amygdala, expression of a truncated form of the TrkB receptor, which blocks the activity of the full-length receptor, blocks both the acquisition of a cued fear (Rattiner et al. 2004b) and extinction of fear (Chhatwal et al. 2006).Although many studies of BDNF in sensory systems have focused on its developmental role, few studies have linked BDNF to learning in the olfactory system, even though the olfactory system at multiple levels shows signs of learning-induced change, including LTP (Ennis et al. 1998;Lebel et al. 2001), dendritic spine plasticity (Knafo et al. 2001), and c-fos activation (Funk and Amir 2000;Schettino and Otto 2001;Illig 2007). In the olfactory system, BDNF is expressed in the olfactory bulb and piriform cortex, and is upregulated in these areas following kainic acid-induced seizures (Katoh-Semba et al. 1999). In slice preparations of the main olfactory bulb, BDNF has been shown to cause an increase in dendritic spines in granule cells (Berghuis et al. 2006). In the piriform cortex, deficits in BDNF have been linked to a decrease in dendritic spine number (Nanobashvili et al. 2005). BDNF is also essential to the differentiation of regenerating cells within the olfactory bulb (Benraiss et al. 2001).No study has yet investigated a...

Differential dynamics of amino acid release in the amygdala and olfactory cortex during odor fear acquisition as revealed with simultaneous high temporal resolution microdialysis

“…In turn, the amygdala sends direct projections back to the piriform cortex (Majak et al 2004). Moreover, the BLA plays a major role in the acquisition, consolidation, and retention of olfactory fear conditioning (Cousens and Otto 1998;Rosenkranz and Grace 2002;Kilpatrick and Cahill 2003;Sevelinges et al 2004Sevelinges et al , 2007Walker et al 2005;Jones et al 2007), thus extending previous observations with auditory and visual CSs to include odor cues. Recent studies also suggest that the posterior piriform cortex (pPCx) may play a critical role in this associative learning (Sevelinges et al 2004(Sevelinges et al , 2008Jones et al 2007).…”

“…Moreover, the BLA plays a major role in the acquisition, consolidation, and retention of olfactory fear conditioning (Cousens and Otto 1998;Rosenkranz and Grace 2002;Kilpatrick and Cahill 2003;Sevelinges et al 2004Sevelinges et al , 2007Walker et al 2005;Jones et al 2007), thus extending previous observations with auditory and visual CSs to include odor cues. Recent studies also suggest that the posterior piriform cortex (pPCx) may play a critical role in this associative learning (Sevelinges et al 2004(Sevelinges et al , 2008Jones et al 2007). Therefore, the olfactory system constitutes a particularly relevant model for studying the relative contribution of sensory cortices and amygdalar nuclei to odor fear learning.…”

De NovoEmergence of Odor Category Representations in the Human Brain

“…4). This remarkable degree of plasticity within the olfactory and limbic systems adds to previous evidence that olfactory perceptual learning can modify both piriform and orbitofrontal activity patterns (Schoenbaum et al, 1999; Sevelinges et al, 2004;Kadohisa and Wilson, 2006;Li et al, 2006;Jones et al, 2007;Roesch et al, 2007;Li et al, 2008;Chapuis et al, 2009), underscoring the idea that odor information content can be dynamically updated in these regions. We also found that category learning-related changes within PPC, pOFC, and INS were specific to the olfactory modality.…”

Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

“…BDNF signaling through its primary receptor TrkB has also been shown to play a significant role in downstream effects underlying learning (36)(37)(38)(39)(40). Previous data from our laboratory have shown increased BDNF transcription and translation in the OB following olfactory fear conditioning (41). Furthermore, OSNs within the MOE express the BDNF receptor TrkB (42).…”