Israela Balderas

The consolidation of object and context recognition memory involve different regions of the temporal lobe

These experiments investigated the involvement of several temporal lobe regions in consolidation of recognition memory. Anisomycin, a protein synthesis inhibitor, was infused into the hippocampus, perirhinal cortex, insular cortex, or basolateral amygdala of rats immediately after the sample phase of object or object-in-context recognition memory training. Anisomycin infused into perirhinal or insular cortices blocked long-term (24 h), but not short-term (90 min) object recognition memory. Infusions into the hippocampus or amygdala did not impair object recognition memory. Anisomycin infused into the hippocampus blocked long-term, but not short-term object-in-context recognition memory, whereas infusions administered into the perirhinal cortex, insular cortex, or amygdala did not affect object-in-context recognition memory. These results clearly indicate that distinct regions of the temporal lobe are differentially involved in long-term object and object-in-context recognition memory. Whereas perirhinal and insular cortices are required for consolidation of familiar objects, the hippocampus is necessary for consolidation of contextual information of recognition memory. Altogether, these results suggest that temporal lobe structures are differentially involved in recognition memory consolidation.

Analysis of the Stress Response in Rats Trained in the Water-Maze: Differential Expression of Corticotropin-Releasing Hormone, CRH-R1, Glucocorticoid Receptors and Brain-Derived Neurotrophic Factor in Limbic Regions

Glucocorticoids and corticotropin-releasing hormone (CRH) are key regulators of stress responses. Different types of stress activate the CRH system; in hypothalamus, CRH expression and release are increased by physical or psychological stressors while in amygdala, preferentially by psychological stress. Learning and memory processes are modulated by glucocorticoids and stress at different levels. To characterize the kind of stress provoked by a hippocampal-dependent task such as spatial learning, we compared the expression profile of glucocorticoid receptor (GR), pro-CRH and CRH-R1 mRNAs (analyzed by RT-PCR), in amygdala, hippocampus and hypothalamus and quantified serum corticosterone levels by radioimmunoassay at different stages of training. mRNA levels of brain-derived neurotrophic factor (BDNF) were also quantified due to its prominent role in learning and memory processes. Male Wistar rats trained for 1, 3 or 5 days in the Morris water-maze (10 trials/day) were sacrificed 5–60 min the after last trial. A strong stress response occurred at day one in both yoked and trained animals (increased corticosterone and hypothalamic pro-CRH and CRH-R1 mRNA levels); changes gradually diminished as the test progressed. In amygdala, pro-CRH mRNA levels decreased while those of BDNF augmented when stress was highest, in yoked and trained animals. Hippocampi, of both yoked and trained groups, had decreased levels of GR mRNA on days 1 and 3, normalizing by day 5, while those of pro-CRH and CRH-R1 increased after the 3rd day. Increased gene expression, specifically due to spatial learning, occurred only for hippocampal BDNF since day 3. These results show that the Morris water-maze paradigm induces a strong stress response that is gradually attenuated. Inhibition of CRH expression in amygdala suggests that the stress inflicted is of physical but not of psychological nature and could lead to reduced fear or anxiety.

Serotonergic versus Nonserotonergic Dorsal Raphe Projection Neurons: Differential Participation in Reward Circuitry

The dorsal raphe nucleus (DRN) contains the largest group of serotonin-producing neurons in the brain and projects to regions controlling reward. Although pharmacological studies suggest that serotonin inhibits reward seeking, electrical stimulation of the DRN strongly reinforces instrumental behavior. Here, we provide a targeted assessment of the behavioral, anatomical, and electrophysiological contributions of serotonergic and nonserotonergic DRN neurons to reward processes. To explore DRN heterogeneity, we used a simultaneous two-vector knockout/optogenetic stimulation strategy, as well as cre-induced and cre-silenced vectors in several cre-expressing transgenic mouse lines. We found that the DRN is capable of reinforcing behavior primarily via nonserotonergic neurons, for which the main projection target is the ventral tegmental area (VTA). Furthermore, these nonserotonergic projections provide glutamatergic excitation of VTA dopamine neurons and account for a large majority of the DRN-VTA pathway. These findings help to resolve apparent discrepancies between the roles of serotonin versus the DRN in behavioral reinforcement.

Taste aversion memory reconsolidation is independent of its retrieval.

Reconsolidation refers to the destabilization/re-stabilization memory process upon its activation. However, the conditions needed to undergo reconsolidation, as well as its functional significance is quite unclear and a matter of intense investigation. Even so, memory retrieval is held as requisite to initiate reconsolidation. Therefore, in the present work we examined whether transient pharmacological disruption of memory retrieval impedes reconsolidation of stored memory in the widely used associative conditioning task, taste aversion. We found that AMPA receptors inhibition in the amygdala impaired retrieval of taste aversion memory. Furthermore, AMPA receptors blockade impeded retrieval regardless of memory strength. However, inhibition of retrieval did not affect anisomycin-mediated disruption of reconsolidation. These results indicate that retrieval is a dispensable condition to undergo reconsolidation and provide evidence of molecular dissociation between retrieval and activation of memory in the non-declarative memory model taste aversion.

Medial temporal lobe structures participate differentially in consolidation of safe and aversive taste memories

Taste memories are amongst the most important kinds of memories, as adequate identification of safe and toxic edibles will determine the subject’s survival. Despite the well‐established role that the medial temporal lobe plays in consolidation of memory, specific contributions of the different regions of the temporal lobe to taste memory consolidation remain unknown. In the present report, we assessed the participation of perirhinal cortex (Ph), dorsal hippocampus (Hipp), basolateral (BLA) and central nuclei of the amygdala (CeA) in safe and aversive taste memories by means of local infusions of the protein synthesis inhibitor anisomycin in the rat. The results showed that protein synthesis in the CeA, but not BLA, is required to stabilize taste aversion memory. Surprisingly, the Ph and Hipp seem to be essential to consolidate safe taste memory. These data suggest that different networks within the temporal lobe are recruited to consolidate memory depending on the consequences associated with tastes.

Cognitive deficits in adult rats by lead intoxication are related with regional specific inhibition of cNOS

It is well known that lead can affect several cognitive abilities in developing animals. In this work, we investigate the effects of different sub-chronic lead doses (0, 65, 125, 250 and 500 ppm of lead acetate in their drinking water for 14 days) in the performance of male adult rats in a water maze, cue maze and inhibitory avoidance tasks. We found that the acquisition of these tasks was not affected by lead, however, the highest dosage of lead (500 ppm) impaired memory consolidation in spatial and inhibitory avoidance tasks, but not in cue maze task while the 250 ppm dose only affected retrieval of spatial memory. Additionally, hippocampal long-term potentiation (LTP) induction in the perforant path after exposing adult rats to different doses of lead was studied. LTP induction was affected in a dose-dependent manner, and treatments of 250 and 500 ppm completely blocked LTP. We investigated the effects of lead intoxication on the activity of constitutive nitric oxide synthase (cNOS) in different brain regions of adult animals. The activity of cNOS was significantly inhibited in the hippocampus and cerebellum but not in the frontal cortex and brain stem, although lead had accumulated in all brain regions. These results suggest that lead intoxication can impair memory in adult animals and this impairment might be related with region-specific effects on cNOS activity.

Retrieval and reconsolidation of object recognition memory are independent processes in the perirhinal cortex.

Reconsolidation refers to the destabilization/re-stabilization process upon memory reactivation. However, the parameters needed to induce reconsolidation remain unclear. Here we evaluated the capacity of memory retrieval to induce reconsolidation of object recognition memory in rats. To assess whether retrieval is indispensable to trigger reconsolidation, we injected muscimol in the perirhinal cortex to block retrieval, and anisomycin (ani) to impede reconsolidation. We observed that ani impaired reconsolidation in the absence of retrieval. Therefore, stored memory underwent reconsolidation even though it was not recalled. These results indicate that retrieval and reconsolidation of object recognition memory are independent processes.

Differential participation of temporal structures in the consolidation and reconsolidation of taste aversion extinction

The extinction process has been described as the decline in the frequency or intensity of the conditioned response following the withdrawal of reinforcement. Hence, experimental extinction does not reflect loss of the original memory, but rather reflects new learning, which in turn requires consolidation in order to be maintained in the long term. During extinction of conditioned taste aversion (CTA), a taste previously associated with aversive consequences acquires a safe status through continuous presentations of the flavor with no aversive consequence. In addition, reconsolidation has been defined as the labile state of a consolidated memory after its reactivation by the presentation of relevant information. In this study, we analyzed structures from the temporal lobe that could be involved in consolidation and reconsolidation of extinction of CTA by means of new protein synthesis. Our results showed that protein synthesis in the hippocampus (HC), the perirhinal cortex (PR) and the insular cortex (IC) of rats participate in extinction consolidation, whereas the basolateral amygdala plays no part in this phenomenon. Furthermore, we found that inhibition of protein synthesis in the IC in a third extinction trial had an effect on reconsolidation of extinction. The participation of the HC in taste memory has been described as a downmodulator for CTA consolidation, and has been related to a context–taste association. Altogether, these data suggest that extinction of aversive taste memories are subserved by the IC, HC and PR, and that extinction can undergo reconsolidation, a process depending only on the IC.

Consolidation and reconsolidation of object recognition memory.

In the first part of this review, we will present evidence showing a functional double dissociation between different structures of the medial temporal lobe in the consolidation of object and object-in-context recognition memory. In addition, we will provide evidence to support this differential participation through protein synthesis inhibitors and neurotransmitters antagonists and agonists. This evidence points out that the perirhinal, prefrontal and insular cortices consolidate the information of individual stimuli, i.e., objects, while the hippocampus consolidates the contextual information where the objects were experimented. In the second part of this review, we will present evidence that shows that the perirhinal cortex is also necessary for reconsolidation of ORM; the destabilization/re-stabilization memory process upon its activation. In the final part of this review, we will present evidence that shows that ORM reconsolidation is an independent process from its retrieval in the perirhinal cortex. Altogether, this review depicts part of the mechanisms by which the medial temporal lobe processes the functional components of recognition memory, in both consolidation and reconsolidation.

Long-term aversive taste memory requires insular and amygdala protein degradation

Some reports have shown that the ubiquitin-proteasome system (UPS) is necessary to degrade repressor factors to produce new proteins essential to memory consolidation. Furthermore, recent evidence suggests that memory updating also relies on protein degradation through the UPS. To evaluate whether degradation of proteins is part of the cellular events needed for long-term storage of taste aversion, we injected lactacystin--an UPS inhibitor--into the amygdala and/or insular cortex 30 min before the first or second training trials. The results revealed that degradation of proteins in either the amygdala or insular cortex suffices for long-term stabilization of first-time encounter taste aversion. On the other hand, lactacystin applied in the insula, but not in the amygdala, before the second training prevented long-term storage of updated information. Our results support that degradation of proteins by means of the UPS is required every time taste aversion is to be stored in long-term memory.