Basolateral amygdala activation enhances object recognition memory by inhibiting anterior insular cortex activity.

Noradrenergic activation of the basolateral amygdala (BLA) by emotional arousal enhances different forms of recognition memory via functional interactions with the insular cortex (IC). Human neuroimaging studies have revealed that the anterior IC (aIC), as part of the salience network, is dynamically regulated during arousing situations. Emotional stimulation first rapidly increases aIC activity but suppresses it in a delayed fashion. Here, we investigated in male Sprague-Dawley rats whether the BLA influence on recognition memory is associated with an increase or suppression of aIC activity during the postlearning consolidation period. We first employed anterograde and retrograde viral tracing and found that the BLA sends dense monosynaptic projections to the aIC. Memory-enhancing norepinephrine administration into the BLA following an object training experience suppressed aIC activity 1 h later, as determined by a reduced expression of the phosphorylated form of the transcription factor cAMP response element-binding (pCREB) protein and neuronal activity marker c-Fos. In contrast, the number of perisomatic γ-aminobutyric acid (GABA)ergic inhibitory synapses per pCREB-positive neuron was significantly increased, suggesting a dynamic up-regulation of GABAergic tone. In support of this possibility, pharmacological inhibition of aIC activity with a GABAergic agonist during consolidation enhanced object recognition memory. Norepinephrine administration into the BLA did not affect neuronal activity within the posterior IC, which receives sparse innervation from the BLA. The evidence that noradrenergic activation of the BLA enhances the consolidation of object recognition memory via a mechanism involving a suppression of aIC activity provides insight into the broader brain network dynamics underlying emotional regulation of memory.

Corticosterone in the dorsolateral striatum facilitates the extinction of stimulus-response memory.

Glucocorticoid hormones are crucially involved in modulating mnemonic processing of stressful or emotionally arousing experiences. They are known to enhance the consolidation of new memories, including those that extinguish older memories. In this study, we investigated whether glucocorticoids facilitate the extinction of a striatum-dependent, and behaviorally more rigid, stimulus-response memory. For this, male rats were initially trained for six days on a stimulus-response task in a T-maze to obtain a reward after making an egocentric right-turn body response, regardless of the starting position in this maze. This training phase was followed by three extinction sessions in which right-turn body responses were not reinforced. Corticosterone administration into the dorsolateral region of the striatum after the first extinction session dose-dependently enhanced the consolidation of extinction memory: Rats administered the higher dose of corticosterone (30 ng), but not lower doses (5 or 10 ng), exhibited significantly fewer right-turn body responses and had longer latencies compared to vehicle-treated animals on the second and third extinction sessions. Co-administration of the glucocorticoid receptor antagonist RU 486 (10 ng) prevented the corticosterone effect, indicating that glucocorticoids enhance the extinction of stimulus-response memory via activation of the glucocorticoid receptor. Corticosterone administration into the dorsomedial striatum did not affect extinction memory. These findings indicate that stress-response mechanisms involving corticosterone actions in the dorsolateral striatum facilitate the extinction of stimulus-response memory that might allow for the development of an opportune behavioral strategy.

Glucocorticoid interactions with the dorsal striatal endocannabinoid system in regulating inhibitory avoidance memory.

The endocannabinoid (eCB) system is highly stress sensitive and known to modulate memory formation of emotionally arousing experiences across different corticolimbic structures. eCB signaling within these circuits is also essentially involved in regulating non-genomically mediated glucocorticoid hormone effects on memory. It has long been thought that the dorsal striatum, which plays a major role in procedural memory and habit formation, is considerably less impacted by stressful experiences; however, recent findings indicate that stress and glucocorticoids also affect striatal-dependent memory processes. Yet, to what extent eCB signaling within the dorsal striatum may mediate such glucocorticoid effects on memory consolidation is currently unknown. Here we show, in male Wistar rats, that the cannabinoid agonist WIN55,212-2 administered into the dorsal striatum immediately after an inhibitory avoidance training experience dose-dependently enhanced 48-h retention performance. Conversely, the cannabinoid type 1 receptor (CB1R) antagonist AM251 impaired retention when administered into the dorsal striatum after inhibitory avoidance training. Most importantly, antagonism of striatal CB1R activity with AM251 completely abolished the effect of corticosterone or of the membrane-impermeable ligand corticosterone:BSA administered posttraining into the dorsal striatum or injected systemically on enhancement of inhibitory avoidance memory. Further, suppression of glucocorticoid signaling by systemic injection of the corticosterone-synthesis inhibitor metyrapone also impaired the memory-enhancing effect of intra-striatal WIN55, 212-2 administration. These findings indicate that the eCB system, in close interaction with glucocorticoid signaling, is involved in modulating plasticity changes underlying memory consolidation not only in corticolimbic structures but also within the dorsal striatum.

Glucocorticoid administration into the dorsolateral but not dorsomedial striatum accelerates the shift from a spatial toward procedural memory.

Glucocorticoid stress hormones are known to enhance the consolidation of hippocampus-dependent spatial and contextual memory. Recent findings indicate that glucocorticoids also enhance the consolidation of procedural memory that relies on the dorsal striatum. The dorsal striatum can be functionally subdivided into the dorsolateral striatum (DLS), which is primarily implicated in shaping procedural memories, and the dorsomedial striatum (DMS), which is engaged in spatial memory. Here, we investigated the hypothesis that posttraining glucocorticoid administration into the DLS promotes the formation of a procedural memory that will normally take place only with extensive training. Male Wistar rats were trained to find a reward in a cross maze that can be solved through either place or response learning. Rats received four trials per day for 5days, a probe trial on Day 6, further training on Days 7-13, and an additional probe trial on Day 14. On Days 2-4 of training, they received posttraining infusions of corticosterone (10 or 30ng) or vehicle into either the DLS or DMS. Rats treated with vehicle into either the DLS or DMS displayed place learning on Day 6 and response learning on Day 14, indicating a shift in control of learned behavior toward a habit-like procedural strategy with extended training. Rats administered corticosterone (10ng) into the DLS displayed response learning on both Days 6 and 14, indicating an accelerated shift to response learning. In contrast, corticosterone administered posttraining into the DMS did not significantly alter the shift from place to response learning. These findings indicate that glucocorticoid administration into the DLS enhances memory consolidation of procedural learning and thereby influences the timing of the switch from the use of spatial/contextual memory to habit-like procedural memory to guide behavior.