Abstract
Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA). However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically-evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex (ACx) and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed with a high ω3 to ω6 PUFA ratio diet (0.97), compared with mice fed with a low ω3 to ω6 PUFA ratio diet (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA diet ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol (2-AG), in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner.
Highlights
Increasing evidence suggests that the ratio of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain may be an important factor in the modulation of emotion
We found that auditory fear memory was reduced after consumption of with high 3:6 ratio diet in a cannabinoid CB1 receptor-dependent manner, and that intake of a high 3:6 ratio diet caused attenuation of long-term potentiation (LTP) in excitatory synaptic transmission at the synapses from the auditory cortex (ACx) to the lateral nucleus of the amygdala (LA)
The current study found that a relatively short-term (6-weeks) intake of a high 3:6 ratio diet causes CB1 receptor–dependent attenuation of LTP in excitatory synaptic transmission at synapses that connect the ACx to the LA
Summary
Increasing evidence suggests that the ratio of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain may be an important factor in the modulation of emotion. PUFA and Synaptic Plasticity membranes was found to be significantly higher in patients with social anxiety disorder compared with control subjects (low ω3 and high ω6; Green et al, 2006). Lifelong deficiency of ω3 PUFA has been found to result in more depression-like behavior in the forced swim test and anxiety-like behaviors in the open field test compared with controls (Lafourcade et al, 2011; Larrieu et al, 2012). Our findings suggested that short-term synaptic plasticity modulated by a CB1 receptor (depolarizationinduced suppression of excitation) was enhanced by with a high 3:6 ratio diet in the basolateral nucleus of the amygdala (BLA; Yamada et al, 2014). Our study did not address whether long-term synaptic plasticity is influenced by a high 3:6 ratio diet
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