Emotional modulation of synapses, circuits and memory.

Abstract

Emotion is a powerful tool for change in the central nervous sys-tem. Whereas, mostlong-term memoriesare stored after practiceor rehearsal, an emotionally arousing memory can be consoli-dated after a single experience. Research examining the influenceof emotion on synaptic function provides a window of oppor-tunity for exploring the mechanisms of memory consolidationduring the minutes to hours after a single, well-rememberedexperience. It can also shed light on numerous psychiatric con-ditions, bringing the field closer to preventing or treating thoseconditions that stem from traumatic memories. This researchtopic brings together leading experts who share their recentfindings and perspectives on how emotion may influence brainfunction.In this issue, four articles review or describe evidence of aspecialized influence of emotion on synaptic function. SheenaJosselyn’slaboratorypreviouslyfoundthatneuronswithhighlev-els of cAMP Responsive Element Binding Protein (CREB) at thetime of training are preferentially allocated to the memory trace(Han et al., 2007). In this issue, Sargin et al. (2013) provide acellular mechanism as to why this may be. They report that over-expression of CREB within neurons of the lateral nucleus of theamygdala (LA), leads to an increase in dendritic spine density,whereas LA neurons with low CREB activity exhibit a decreaseindendriticspinedensity.ThesedatasupportthehypothesisthatCREB may increase a neuron’s propensity for being included in amemory trace by increasing dendritic spine density.Young and Williams addressed the issue of lateralization ofamygdala recruitment during memory consolidation. Imagingstudies in humans indicate that activity in the right amygdala isassociated with aversive memories (Morris et al., 1999). Othersindicatethattheleftamygdalaispreferentiallyinvolvedinencod-ing memories that have a positive valence (Zalla et al., 2000;Hamann et al., 2002). In this issue, Young and Williams (2013)examine expression of a marker of synaptic plasticity in the ratamygdala. They report that the synaptic plasticity-related pro-tein Arc is specifically elevated in the right amygdala followingtraining on an aversive task, and in the left amygdala followingtraining on an appetitive task. Considering that Arc expressionin the amygdala is necessary for consolidation of conditionedfear (Ploski et al., 2008), these findings indicate that, memory-related synaptic plasticity in the amygdala is lateralized andvalence-dependent.Headley and Pare (2013) add a temporal dimension to thisresearch topic. They review literature on temporal synchronyof firing across brain regions involved in emotional memory.They describe gamma oscillations and emotional memory, citingrecent reports of enhanced gamma oscillations in the neocor-tex and amygdala during emotional situations, and evidence thatgamma oscillations have predictive value for synaptic plasticityand emotional memory.Gronli et al. (2013) take a different view on the effects ofemotion on memory and plasticity. These authors review thecellular and molecular evidence that stress may impair cogni-tion by interfering with sleep. They describe the importance ofsleep for the cellular and molecular processes that contribute tomemoryconsolidation,andsuggestthatstressthatinterfereswithsleep is associated with deficient synaptic plasticity and impairedcognitive performance.Several of the contributions to this issue examined synapticchanges related to extinction of conditioned fear in rats. Bothpost-traumatic stress disorder (PTSD) and obsessive compulsivedisorder (OCD) are characterized by avoidance of stimuli thatare perceived as threatening, even in the absence of real dan-ger. Impaired extinction of conditioned fear could contributeto the persistence of maladaptive behaviors seen in these dis-orders (Milad et al., 2008, 2013). It was recently demonstratedthat vagus nerve stimulation (VNS) enhances extinction of con-ditioned fear in rats (Pena et al., 2013). In this issue, (Pena etal.,2014)reportthatextinction-enhancingVNSreversessynapticdepression in the infralimbic prefrontal cortex basolateral amyg-dala pathway, a circuit that is implicated in extinction memory(Sierra-Mercado et al., 2011). Collectively, these findings sug-gest that VNS could be paired with exposure therapy to facilitateextinction of conditioned fear and reverse pathological synap-tic function seen in anxiety disorders. Another contributioninvestigated the effects of deep brain stimulation (DBS) on theextinction circuitry. In 2010, several groups reported that stimu-lation of the ventral capsule/ventral striatum reduced symptomsofOCDinrefractorypatients(Denysetal.,2010;Goodmanetal.,2010; Greenberg et al., 2010). In rats, stimulation of the ventralstriatum enhances extinction of conditioned fear (Rodriguez-Romaguera et al., 2012). In this issue, research from Greg Quirk’slab demonstrates that extinction-enhancing stimulation of theventral striatum increases expression of the brain-derived neu-rotrophic factor protein (BDNF) in the medial prefrontal cortex,indicating that the clinical benefits of DBS may be mediatedby BDNF-associated synaptic changes in the extinction pathway(Do-Monte et al., 2013).One of the limitations of exposure therapy is that condi-tionedfearcanreturnevenaftersuccessfulextinctionlearning.In