Muscarinic cholinergic influences in memory consolidation

The central cholinergic system and muscarinic cholinergic receptor (mR) activation have long been associated with cognitive function. Although mR activation is no doubt involved in many aspects of cognitive functioning, the extensive evidence that memory is influenced by cholinergic treatments given after training either systemically or intra-cranially clearly indicates that cholinergic activation via mRs is a critical component in modulation of memory consolidation. Furthermore, the evidence indicates that activation of mRs in the basolateral amygdala (BLA) plays an essential role in enabling other neuromodulatory influences on memory consolidation. Memory can also be affected by posttraining activation of mRs in the hippocampus, striatum and cortex. Evidence of increases in hippocampal and cortical acetylcholine (ACh) levels following learning experiences support the view that endogenous ACh release is involved in long-term memory consolidation. Furthermore, the findings indicating that mR drug treatments influence plasticity in the hippocampus and in sensory cortices strongly suggest that mR activation is involved in the storage of information in these brain regions.     

Enhancement of extinction memory consolidation: the role of the noradrenergic and GABAergic systems within the basolateral amygdala

Evidence from previous studies indicates that the noradrenergic and GABAergic influences within the basolateral amygdala (BLA) modulate the consolidation of memory for fear conditioning. The present experiments investigated whether the same modulatory influences are involved in regulating the extinction of fear-based learning. To investigate this issue, male Sprague Dawley rats implanted with unilateral or bilateral cannula aimed at the BLA were trained on a contextual fear conditioning (CFC) task and 24 and 48 h later were given extinction training. Immediately following each extinction session they received intra-BLA infusions of the GABAergic antagonist bicuculline (50 ng), the beta-adrenocepter antagonist propranolol (500 ng), bicuculline with propranolol, norepinephrine (NE) (0.3, 1.0, and 3.0 microg), the GABAergic agonist muscimol (125 ng), NE with muscimol or a control solution. To investigate the involvement of the dorsal hippocampus (DH) as a possible target of BLA activation during extinction, other animals were given infusions of muscimol (500 ng) via an ipsilateral cannula implanted in the DH. Bilateral BLA infusions of bicuculline significantly enhanced extinction, as did infusions into the right, but not left BLA. Propranolol infused into the right BLA together with bicuculline blocked the bicuculline-induced memory enhancement. Norepinephrine infused into the right BLA also enhanced extinction, and this effect was not blocked by co-infusions of muscimol. Additionally, muscimol infused into the DH did not attenuate the memory enhancing effects of norepinephrine infused into the BLA. These findings provide evidence that, as with original CFC learning, noradrenergic activation within the BLA modulates the consolidation of CFC extinction. The findings also suggest that the BLA influence on extinction is not mediated by an interaction with the dorsal hippocampus.     

Microinfusions of flumazenil into the basolateral but not the central nucleus of the amygdala enhance memory consolidation in rats.

Extensive evidence indicates that benzodiazepine receptors in the amygdala are involved in regulating memory consolidation. Recent findings indicate that many other drugs and hormones influence memory through selective activation of the basolateral amygdala nucleus (BLA). This experiment examined whether the memory-modulatory effect of flumazenil, a benzodiazepine receptor antagonist, selectively involves the BLA. Bilateral microinfusions of flumazenil (12 nmol in 0.2 microl) into the BLA of rats administered immediately after training in an inhibitory avoidance task significantly enhanced 48-h retention performance whereas infusions into the central nucleus were ineffective. These findings indicate that the BLA is selectively involved in mediating flumazenil's influence on memory storage and are thus consistent with extensive evidence indicating that the BLA is involved in regulating memory consolidation.     

Post-training intra-basolateral amygdala infusions of norepinephrine block sevoflurane-induced impairment of memory consolidation and activity-regulated cytoskeletal protein expression inhibition in rat hippocampus

Considerable evidence indicates that the noradrenergic system of the basolateral amygdala (BLA) participates in the consolidation of various types of emotionally arousing memories. We previously reported that administration of an anesthetic-dose of sevoflurane immediately after continuous multiple-trail inhibition avoidance (CMIA) training impaired memory consolidation. This experiment investigated whether posttraining noradrenergic activation of the BLA is sufficient to reverse the memory impairing effect of sevoflurane. Adult male Sprague-Dawley rats received bilateral injections of norepinephrine (NE 0.3, 1.0, or 3.0 μg/0.5 μl) or normal saline (NS 0.5 μl) immediately after training in a CMIA paradigm. Subsequently, the rats were exposed to sevoflurane (2% inspired) or air for 2h. Norepinephrine produced a dose-dependent enhancement of memory consolidation on a 24-h retention test. The highest dose of NE tested (3.0 μg/0.5 μl) blocked sevoflurane-induced impairment of memory consolidation and reversed the inhibitory effect of sevoflurane on activity-regulated cytoskeletal protein (Arc) expression in the hippocampus 2h after training. These findings provide evidence that the mechanism mediating the memory-impairing effect of sevoflurane involves a network interaction between the BLA noradrenergic system and modulation of Arc protein expression in the hippocampus.     

情绪唤醒影响记忆巩固过程的神经生理机制

白鼠和人类都对情绪唤醒的经历有更好的记忆。情绪唤醒影响记忆巩固的神经生理机制主要有以下几种方式:(a)情绪唤醒或急性应激,会引发个体内部应激激素的释放,从而增强其记忆巩固过程。(b1)杏仁核的激活对情绪唤醒影响记忆巩固过程十分重要,杏仁核内部去甲肾上腺素(NE)的释放影响记忆巩固过程。(b2)杏仁核投射到负责不同类型记忆加工的脑区,如海马和皮层,从而影响记忆。(c)应激激素影响记忆巩固的过程中,杏仁核内NE的激活在这一过程中扮演着重要角色。综上,情绪唤醒影响记忆巩固的过程,涉及到激素调节、神经调节及二者的共同作用。     

Orphanin FQ/nociceptin interacts with the basolateral amygdala noradrenergic system in memory consolidation

Extensive evidence indicates that the basolateral complex of the amygdala (BLA) mediates hormonal and neurotransmitter effects on the consolidation of emotionally influenced memory and that such modulatory influences involve noradrenergic activation of the BLA. As the BLA also expresses a high density of receptors for orphanin FQ/nociceptin (OFQ/N), an opioid-like peptide with anxiolytic and amnestic properties, the present experiments investigated whether the BLA is involved in mediating OFQ/N effects on memory consolidation and whether such effects require noradrenergic activity. OFQ/N (0.01-100 pmol in 0.2 microL) administered bilaterally into the BLA of male Sprague-Dawley rats immediately after aversively motivated inhibitory avoidance training induced dose-dependent impairment on a 48-h retention trial. The beta(1)-adrenoceptor antagonist atenolol (2.0 nmol) administered concurrently into the BLA potentiated the dose-response effects of OFQ/N. In contrast, immediate post-training infusions of the peptidergic OFQ/N receptor antagonist [Nphe(1)]nociceptin(1-13)NH(2) (1-100 pmol in 0.2 microL) into the BLA enhanced 48-h retention of inhibitory avoidance training, an effect that was blocked by coadministration of atenolol. Delayed infusions of OFQ/N or [Nphe(1)]nociceptin(1-13)NH(2) into the BLA administered either 6 or 3 h after training, respectively, or immediate post-training infusions of OFQ/N into the adjacent central amygdala did not significantly alter retention performance. These findings indicate that endogenously released OFQ/N interacts with noradrenergic activity within the BLA in modulating memory consolidation.     

Involvement of the basolateral amygdala in muscarinic cholinergic modulation of extinction memory consolidation

Previous studies have reported that drugs affecting neuromodulatory systems within the basolateral amygdala (BLA), including drugs affecting muscarinic cholinergic receptors, modulate the consolidation of many kinds of training, including contextual fear conditioning (CFC). The present experiments investigated the involvement of muscarinic cholinergic influences within the BLA in modulating the consolidation of CFC extinction memory. Male Sprague Dawley rats implanted with unilateral cannula aimed at the BLA were trained on a CFC task, using footshock stimulation, and 24 and 48 h later were given extinction training by replacing them in the apparatus without footshock. Following each extinction session they received intra-BLA infusions of the cholinergic agonist oxotremorine (10 ng). Immediate post-extinction BLA infusions significantly enhanced extinction but infusions administered 180 min after extinction training did not influence extinction. Thus the oxotremorine effects were time-dependent and not attributable to non-specific effects on retention performance. These findings provide evidence that, as previously found with original CFC learning, cholinergic activation within the BLA modulates the consolidation of CFC extinction.     

Enhancement of inhibitory avoidance and conditioned taste aversion memory with insular cortex infusions of 8-Br-cAMP: involvement of the basolateral amygdala

There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the acquisition/consolidation of conditioned taste aversion (CTA). Posttraining infusion into the IC of 0.3 microg oxotremorine and 1.25 microg 8-Br-cAMP enhanced IA retention. Infusions of 8-Br-cAMP, but not oxotremorine, into the IC enhanced taste aversion. The experiments also examined whether noradrenergic activity in the basolateral amygdala (BLA) is critical in enabling the enhancement of CTA and IA memory induced by drug infusions administered into the IC. For both CTA and IA, ipsilateral infusions of beta-adrenergic antagonist propranolol administered into the BLA blocked the retention-enhancing effect of 8-Br-cAMP or oxotremorine infused into the IC. These results indicate that the IC is involved in the consolidation of memory for both IA and CTA, and this effect requires intact noradrenergic activity into the BLA. These findings provide additional evidence that the BLA interacts with other brain regions, including sensory cortex, in modulating memory consolidation.     

Noradrenergic activation of the basolateral amygdala modulates consolidation of object recognition memory

Noradrenergic activation of the basolateral complex of the amygdala (BLA) modulates the consolidation of memory for many kinds of highly emotionally arousing training tasks. The present experiments investigated whether posttraining noradrenergic activation of the BLA is sufficient to enable memory consolidation of a low-arousing training experience. Sprague-Dawley rats received intra-BLA infusions of norepinephrine, the beta-adrenoceptor antagonist propranolol or saline immediately after either 3 or 10 min of object recognition training. Saline-infused controls exhibited poor 24-h retention when given 3 min of object recognition training and good retention when given 10 min of training. Norepinephrine administered after 3 min of object recognition training produced dose-dependent enhancement of 24-h object recognition memory whereas propranolol administered after 10 min of training produced dose-dependent impairment of memory. These findings provide evidence that posttraining noradrenergic activation of the BLA enhances memory of a low-arousing training experience that would otherwise not induce long-term memory. Thus, regardless of the degree of emotional arousal induced by an experience, noradrenergic activation of the BLA after the experience ensures that it will be better remembered.     

Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in chronic anxiety

Stress initiates a series of neuronal responses that prepare an organism to adapt to new environmental challenges. However, chronic stress may lead to maladaptive responses that can result in psychiatric syndromes such as anxiety and depressive disorders. Corticotropin-releasing factor (CRF) has been identified as a key neuropeptide responsible for initiating many of the endocrine, autonomic and behavioral responses to stress. The amygdala expresses high concentrations of CRF receptors and is itself a major extrahypothalamic source of CRF containing neurons. Within the amygdala, the basolateral nucleus (BLA) has an important role in regulating anxiety and affective responses. During periods of stress, CRF is released into the amygdala and local CRF receptor activation has been postulated as a substrate for stress-induced alterations in affective behavior. Previous studies have suggested that synaptic plasticity in the BLA contributes to mechanisms underlying long-term changes in the regulation of affective behaviors. Several studies have shown that acute glutamate receptor-mediated activation, by either GABA-mediated disinhibition or CRF-mediated excitation, induces long-term synaptic plasticity and increases the excitability of BLA neurons. This review summarizes some of the data supporting the hypotheses that stress induced plasticity within the amygdala may be a critical step in the pathophysiology of the development of chronic anxiety states. It is further proposed that such a change in the limbic neural circuitry is involved in the transition from normal vigilance responses to pathological anxiety, leading to syndromes such as panic and post-traumatic stress disorders.     

Biphasic ERK1/2 activation in both the hippocampus and amygdala may reveal a system consolidation of contextual fear memory

There is accumulating evidences to suggest that memory consolidation in some conditions involves two waves of neuronal plastic change. Using two fear conditioning procedures in male C57BL/6J mice, we have recently shown that consolidation of the foreground contextual fear memory required two waves of ERK1/2 activation in hippocampal CA1, while consolidation of cue conditioning was only associated with the early phase of activation. The present experiment further showed that this bi-phasic pattern of ERK1/2 activation was not restricted to hippocampal CA1, but could also be observed in other fear memory-related brain areas. The unpaired conditioning procedure (context in foreground) induced two waves of ERK1/2 activation in hippocampal CA1 and CA3, as well as in the LA and BLA nuclei of the amygdala. In contrast, the paired conditioning procedure (context in background) led to a transient early phase only in hippocampal CA1 and LA. In addition, ERK1/2 phosphorylation in the hippocampus was found to correlate with that in the amygdala nuclei specifically after the unpaired procedure. Taken together, our data suggest that the observed biphasic pattern of neuronal plastic events may reflect the interplay between hippocampal and amygdala activity-dependent plasticity critical for the system consolidation of contextual fear memory.     

Memory-enhancing corticosterone treatment increases amygdala norepinephrine and Arc protein expression in hippocampal synaptic fractions

Considerable evidence indicates that glucocorticoid hormones enhance the consolidation of memory for emotionally arousing events through interactions with the noradrenergic system of the basolateral complex of the amygdala (BLA). We previously reported that intra-BLA administration of a β-adrenoceptor agonist immediately after inhibitory avoidance training enhanced memory consolidation and increased hippocampal expression of the protein product of the immediate early gene activity-regulated cytoskeletal-associated protein (Arc). In the present experiments corticosterone (3 mg/kg, i.p.) was administered to male Sprague-Dawley rats immediately after inhibitory avoidance training to examine effects on long-term memory, amygdala norepinephrine levels, and hippocampal Arc expression. Corticosterone increased amygdala norepinephrine levels 15 min after inhibitory avoidance training, as assessed by in vivo microdialysis, and enhanced memory tested at 48 h. Corticosterone treatment also increased expression of Arc protein in hippocampal synaptic tissue. The elevation in BLA norepinephrine appears to participate in corticosterone-influenced modulation of hippocampal Arc expression as intra-BLA blockade of β-adrenoceptors with propranolol (0.5 μg/0.2 μL) attenuated the corticosterone-induced synaptic Arc expression in the hippocampus. These findings indicate that noradrenergic activity at BLA β-adrenoceptors is involved in corticosterone-induced enhancement of memory consolidation and expression of the synaptic-plasticity-related protein Arc in the hippocampus.     

Mapping of olfactory memory circuits: region-specific c-fos activation after odor-reward associative learning or after its retrieval

Although there is growing knowledge about intracellular mechanisms underlying neuronal plasticity and memory consolidation and reconsolidation after retrieval, information concerning the interaction among brain areas during formation and retrieval of memory is relatively sparse and fragmented. Addressing this question requires simultaneous monitoring of activity in multiple brain regions during learning, the post-acquisition consolidation period, and retrieval and subsequent reconsolidation. Immunoreaction to the immediate early gene c-fos is a powerful tool to mark neuronal activation of specific populations of neurons. Using this method, we are able to report, for the first time, post-training activation of a network of closely related brain regions, particularly in the frontal cortex and the basolateral amygdala (BLA), that is specific to the learning of an odor-reward association. On the other hand, retrieval of a well-established associative memory trace does not seem to differentially activate the same regions. The amygdala, in particular, is not engaged after retrieval, whereas the lateral habenula (LHab) shows strong activation that is restricted to animals having previously learned the association. Although intracellular mechanisms may be similar during consolidation and reconsolidation, this study indicates that different brain circuits are involved in the two processes, at least with respect to a rapidly learned olfactory task.     

Modulation of memory consolidation by the basolateral amygdala or nucleus accumbens shell requires concurrent dopamine receptor activation in both brain regions

Previous findings indicate that the basolateral amygdala (BLA) and the nucleus accumbens (NAc) interact in influencing memory consolidation. The current study investigated whether this interaction requires concurrent dopamine (DA) receptor activation in both brain regions. Unilateral, right-side cannulae were implanted into the BLA and the ipsilateral NAc shell or core in male Sprague-Dawley rats ( approximately 300 g). One week later, the rats were trained on an inhibitory avoidance (IA) task and, 48 h later, they were tested for retention. Drugs were infused into the BLA and NAc shell or core immediately after training. Post-training intra-BLA infusions of DA enhanced retention, as assessed by latencies to enter the shock compartment on the retention test. Infusions of the general DA receptor antagonist cis-Flupenthixol (Flu) into the NAc shell (but not the core) blocked the memory enhancement induced by the BLA infusions of DA. In the reverse experiment, post-training intra-NAc shell infusions of DA enhanced retention and Flu infusions into the BLA blocked the enhancement. These findings indicate that BLA modulation of memory consolidation requires concurrent DA receptor activation in the NAc shell but not the core. Similarly, NAc shell modulation of memory consolidation requires concurrent DA receptor activation in the BLA. Together with previous findings, these results suggest that the dopaminergic innervation of the BLA and NAc shell is critically involved in the modulation of memory consolidation.     

Nitric oxide synthesis in the basolateral complex of the amygdala is required for the consolidation and expression of fear potentiated startle but not shock sensitization of the acoustic startle

Nitric oxide (NO) is synthesized as a result of N-methyl-d-asparate (NMDA) receptor activation, it acts as an retrograde neurotransmitter freely diffusing across cell membranes interacting with its targets in a non-synaptic manner. Consequently, NO has been described as an extension of NMDA receptor activation. The targets of NO include cellular components within the basolateral complex of the amygdala (BLA) that are necessary for the consolidation of conditioned fear as well as targets that can significantly modulate neurotransmission associated with its expression. Given that both are NMDA receptor associated processes, this implies that NO may be an important intermediary of NMDA receptor activation and both fear memory consolidation and expression. The current study sought to examine this using visual fear conditioning and fear potentiated startle. Three experiments were conducted, rats received intra-BLA microinfusions of the global nitric oxide synthase inhibitor l-NAME either prior to fear conditioning, or expression of learned fear. Furthermore, NO's ability to modulate a NMDA receptor independent fear process was assessed by microinfusing l-NAME into the BLA prior to examination of the shock sensitization of the acoustic startle affect. The results indicated that NO was, indeed, required for both the consolidation and expression of learned fear, whereas it was not required for NMDA independent shock enhanced startle responding. This study illustrates that NO plays a pivotal role in the examined NMDA associated fear processes.     

Impaired emotional declarative memory following unilateral amygdala damage

Case studies of patients with bilateral amygdala damage and functional imaging studies of normal individuals have demonstrated that the amygdala plays a critical role in encoding emotionally arousing stimuli into long-term declarative memory. However, several issues remain poorly understood: the separate roles of left and right amygdala, the time course over which the amygdala participates in memory consolidation, and the type of knowledge structures it helps consolidate. We investigated these questions in eight subjects with unilateral amygdala damage, using several different measures. For comparison, our main task used stimuli identical to those used previously to investigate emotional declarative memory in patients with bilateral amygdala damage. Contrasts with both brain-damaged and normal control groups showed that subjects with left amygdala damage were impaired in their memory for emotional stimuli, despite entirely normal memory for neutral stimuli (because of a number of caveats, the findings from subjects with right amygdala damage were less clear). Follow-up experiments suggested that the normal facilitation of memory for emotional stimuli may develop over an extended time course (>30 min), consistent with prior findings, and that the specific impairment we report may depend in part on the lexical nature of the task used (written questionnaire). We stress the complex and temporally extended nature of memory consolidation and suggest that the amygdala may influence specific components of this process.     

On the requirement of nitric oxide signaling in the amygdala for consolidation of inhibitory avoidance memory

Evidence suggests that the NO/sGC/PKG pathway plays a key role in memory processing but the actual participation of this signaling cascade in the amygdala during memory consolidation remains unknown. Here, we show that when infused in the amygdala immediately after inhibitory avoidance training, but not later, the NO synthase inhibitor L-NNA hindered long-term memory retention without affecting locomotion, exploratory behavior, anxiety state or retrieval of the avoidance response. The amnesic effect of L-NNA was not state-dependent and was mimicked by the soluble guanylyl cyclase inhibitor LY83583 and the PKG inhibitor KT-5823. On the contrary, post-training intra-amygdala infusion of the NOS substrate L-Arg, the NO-releasing compound SNAP or the non-hydrolysable analog of cGMP 8Br-cGMP increased memory retention in a dose-dependent manner. Co-infusion of 8Br-cGMP reversed the amnesic effect of L-NNA and LY83583 but not that of KT-5823. Our data indicate that the NO-induced activation of PKG in the amygdala is a necessary step for consolidation of inhibitory avoidance memory.     

Memory enhancement induced by post-training intrabasolateral amygdala infusions of beta-adrenergic or muscarinic agonists requires activation of dopamine receptors: Involvement of right, but not left, basolateral amygdala

Previous findings indicate that the noradrenergic, dopaminergic, and cholinergic innervations of the basolateral amygdala (BLA) modulate memory consolidation. The current study investigated whether memory enhancement induced by post-training intra-BLA infusions of a beta-adrenergic or muscarinic cholinergic agonist requires concurrent activation of dopamine (DA) receptors in the BLA. Rats with implanted BLA cannulae were trained on an inhibitory avoidance (IA) task and, 48 h later, tested for retention. Infusions of the beta-adrenergic agonist clenbuterol into the right BLA, but not the left, enhanced retention, and concurrent infusions of the nonspecific DA receptor antagonist cis-Flupenthixol (Flu) blocked the enhancement. Post-training infusions of the muscarinic agonist oxotremorine into the right BLA also enhanced retention, and concurrent infusions of Flu blocked this effect. Additional experiments investigated whether memory modulation was lateralized to the right BLA. Post-training DA infusions into the right BLA, but not the left, enhanced retention. Post-training infusions of lidocaine or muscimol, which impair retention when infused bilaterally, had no effect when infused unilaterally into either the right or left BLA. These findings, together with earlier work, suggest that the dopaminergic system in the BLA is critically involved in memory modulation induced by noradrenergic and cholinergic influences. Additionally, these findings indicate that the enhancement, but not impairment, of memory consolidation is lateralized to the right BLA.     

The effects of post-encoding stress on recognition memory: examining the impact of skydiving in young men and women

Prior studies have indicated that post-encoding stress can protect memories from the effects of forgetting, and this has been taken as evidence that stress facilitates memory consolidation. However, it is not known whether stress acts by directly influencing the strength of the underlying memories or whether it influences the generation process that plays a critical role in tests such as free recall. To address this issue, we examined the effects of stress produced by skydiving on recognition memory for negative and neutral pictures. Relative to a non-stress control condition, post-encoding stress in males was found to increase recognition memory for neutral pictures. However, stress was not found to improve recognition for emotional pictures, nor was it found to influence recognition memory in female participants. Additional analysis of recognition performance suggested that stress increased familiarity-based recognition rather than recollection. This study indicates that stress can improve familiarity-based recognition, thus showing that stress directly increases the strength of the underlying memories.     

Involvement of the rostral anterior cingulate cortex in consolidation of inhibitory avoidance memory: interaction with the basolateral amygdala

Previous findings suggest that the rostral anterior cingulate cortex (rACC) is involved in memory for emotionally arousing training. There is also extensive evidence that the basolateral amygdala (BLA) modulates the consolidation of emotional arousing training experiences via interactions with other brain regions. The present experiments examined the effects of posttraining intra-rACC infusions of the cholinergic agonist oxotremorine (OXO) on inhibitory avoidance (IA) retention and investigated whether the BLA and rACC interact in enabling OXO effects on memory. In the first experiment, male Sprague-Dawley rats were implanted with bilateral cannulae above the rACC and given immediate posttraining OXO infusions. OXO (0.5 or 3 ng) induced significant enhancement of retention performance on a 48-h test. In the second experiment, unilateral posttraining OXO infusions (0.5, 3.0 or 10 ng) enhanced retention when infused into rACC, but not caudal ACC, consistent with previous evidence that ACC is composed of functionally distinct regions. A third experiment investigated the effects of posttraining intra-rACC OXO infusions (0.5 or 10 ng) in rats with bilateral sham or NMDA-induced lesions of the BLA. The BLA lesions did not impair IA retention, but blocked the enhancement induced by posttraining intra-rACC OXO infusions. Lastly, unilateral NMDA lesions of rACC blocked the enhancement of IA retention induced by posttraining ipsilateral OXO infusions into the BLA. These findings support the hypothesis that the rACC is involved in modulating the storage of emotional events and provide additional evidence that the BLA modulates memory consolidation through interactions with efferent brain regions, including the cortex.