Social Memory and the Role of the Hippocampal CA2 Region

The CA2 region of the hippocampus is a somewhat obscure area lacking in an understanding of its form and function. Until recently, the CA2 has been thought of as merely an extension of the CA3, with some referring to it as the CA3a region. Recent investigations into this area have not only delineated the CA2, but also defined it as a region distinct from both CA1 and CA3, with a unique set of cortical inputs and outputs and contributions to cognitive processes. One such process that has been shown to depend on the CA2 is the ability to recognize a novel or familiar conspecific, known as social recognition memory. Here, we review these findings and discuss the parallels between CA2 dysfunction and social impairments

Memory enhancement produced by post-training exposure to sucrose-conditioned cues

A number of aversive and appetitive unconditioned stimuli (such as shock and food) are known to produce memory enhancement when they occur during the post-training period. Post-training exposure to conditioned aversive stimuli has also been shown to enhance memory consolidation processes. The present study shows for the first time that post-training exposure to conditioned stimuli previously paired with consumption of a sucrose solution also enhances memory consolidation. Male Long Evans rats were trained on a one-session conditioned cue preference (CCP) task on a radial arm maze. Immediately or 2 hours after training, rats consumed a sucrose solution or were exposed to cues previously paired with consumption of sucrose or cues previously paired with water. Twenty-four hours later, the rats were tested for a CCP. Immediate, but not delayed, post-training consumption of sucrose enhanced memory for the CCP. Immediate, but not delayed, post-training exposure to cues previously paired with sucrose, but not with water, also enhanced CCP memory. The possibility that rewarding and aversive conditioned stimuli affect memory by a common physiological process is discussed

Circannual changes in stress and feeding hormones and their effect on food-seeking behaviors

Seasonal fluctuations in food availability show a tight association with seasonal variations in body weight and food intake. Seasonal variations in food intake, energy storage, and expenditure appear to be a widespread phenomenon suggesting they may have evolved in anticipation for changing environmental demands. These cycles appear to be driven by changes in external daylength acting on neuroendocrine pathways. A number of neuroendocrine pathways, two of which are the endocrine mechanisms underlying feeding and stress, appear to show seasonal changes in both their circulating levels and reactivity. As such, variation in the level or reactivity to these hormones may be crucial factors in the control of seasonal variations in food-seeking behaviors. The present review examines the relationship between feeding behavior and seasonal changes in circulating hormones. We hypothesize that seasonal changes in circulating levels of glucocorticoids and the feeding-related hormones ghrelin and leptin contribute to seasonal fluctuations in feeding-related behaviors. This review will focus on the seasonal circulating levels of these hormones as well as sensitivity to these hormones in the modulation of food-seeking behaviors

The impact of multiple memory formation on dendritic complexity in the hippocampus and anterior cingulate cortex assessed at recent and remote time points

Consolidation processes, involving synaptic and systems level changes, are suggested to stabilize memories once they are formed. At the synaptic level, dendritic structural changes are associated with long-term memory storage. At the systems level, memory storage dynamics between the hippocampus and anterior cingulate cortex (ACC) may be influenced by the number of sequentially encoded memories. The present experiment utilized Golgi-Cox staining and neuron reconstruction to examine recent and remote structural changes in the hippocampus and ACC following training on three different behavioral procedures. Rats were trained on one hippocampal-dependent task only (a water maze task), two hippocampal-dependent tasks (a water maze task followed by a radial arm maze task), or one hippocampal-dependent and one non-hippocampal-dependent task (a water maze task followed by an operant conditioning task). Rats were euthanized recently or remotely. Brains underwent Golgi-Cox processing and neurons were reconstructed using Neurolucida software (MicroBrightField, Williston, VT, USA). Rats trained on two hippocampal-dependent tasks displayed increased dendritic complexity compared to control rats, in neurons examined in both the ACC and hippocampus at recent and remote time points. Importantly, this behavioral group showed consistent, significant structural differences in the ACC compared to the control group at the recent time point. These findings suggest that taxing the demand placed upon the hippocampus, by training rats on two hippocampal-dependent tasks, engages synaptic and systems consolidation processes in the ACC at an accelerated rate for recent and remote storage of spatial memories

Preadolescent exposure to a sexually mature, unrelated male rat reduces postadolescent social recognition memory and CA2 c-Fos labeling

IntroductionSocial memory involves social recognition: the ability to discriminate between two or more conspecifics when one has been previously encountered. The CA2 region of the hippocampus has been implicated in social memory, as lesions and dysfunction to this area lead to social memory impairments. A variety of psychogenic manipulations during postnatal sensitive developmental periods are associated with social memory impairments later in life.MethodsIn this study, we exposed preadolescent rats to a sexually, mature unrelated male and examined whether this was associated with changes in postadolescent social memory and c-Fos labeling in the CA2 region. Male and female Long-Evans rats were exposed to a male, adult rat on postnatal days 19–21 (P19–21). Social memory was measured during the postadolescent period and defined as increased interactions towards a novel age-matched rat in contrast to a previously-encountered age-matched rat. After the test, rats were euthanized and brain tissue was then collected to quantify c-Fos labeling within the CA2 region.ResultsCompared to home cage controls and controls not exposed to the adult male, male and female rats exposed to the unrelated adult during preadolescence were unable to discriminate between a novel and previously encountered conspecific during the postadolescent test showing social memory deficits. The groups that showed social recognition deficits also had significantly fewer c-Fos-positive cells within the CA2 region compared to the control groups.DiscussionThese findings indicate that threatening psychogenic encounters during preadolescence can have detrimental long-term effects on social memory potentially via disrupted activity in the CA2 hippocampal region

Comparison of the Time-Dependent Changes in Immediate Early Gene Labeling and Spine Density Following Abstinence From Contingent or Non-contingent Chocolate Pellet Delivery

Rationale: Incubation of craving is a phenomenon whereby responding for cues associated with a reward increases over extended periods of abstinence. Both contingent and non-contingent behavioral designs have been used to study the incubation of craving phenomenon with differing results. The present study directly compares behavioral and neural changes following contingent or non-contingent administration of chocolate flavored pellets.Objective: The current study examined whether an incubation of craving response would be observed at the behavioral and neural levels following delays of abstinence from chocolate pellets in a contingent or non-contingent reinforcement design.Methods: Rats were trained for 10 days to bar press for chocolate pellets (contingent) or received chocolate pellets in a non-contingent design (classical conditioning). Groups were then subjected to abstinence from the reward for 24 h, 7, 14 or 28 days at which point they were tested for responding for reward associated cues. Following the test, brains from all rats were processed and assessed for c-Fos and FosB labeling as well as dendritic spine density in the nucleus accumbens (NAc).Results: Behavioral measures during the test (lever presses, food hopper entries and locomotor activity) revealed similar behavioral outcomes across all delays indicating the lack of an incubation of craving response on both the contingent and non-contingent designs. Overall, labeling of c-Fos in the NAc was lower for the non-contingent group compared to the operant-trained and food restricted control. Compared to the operant-trained and non-trained control groups, a significantly reduced FosB labeling was noted in the NAc of the classically conditioned groups across all abstinence periods. Spine density in the NAc was elevated in both the classically and operant conditioned compared to the food-restricted, non-trained controls.Conclusions: Chocolate pellet reward did not result in incubation of craving but did produce behavioral learning that was associated with increased spine density. This suggests that chocolate pellet administration results in long-term structural and functional changes that are present for at least 28 days following abstinence. Contingent and non-contingent administration resulted in differential immediate early gene labeling in the NAc, but the functional significance of this has yet to be elucidated

Developmental Aspects of Glucose and Calcium Availability on the Persistence of Memory Function Over the Lifespan

An important aspect concerning the underlying nature of memory function is an understanding of how memories are acquired and lost. The stability, and ultimate demise, of memory over the lifespan of an organism remains a critical topic in determining the neurobiological mechanisms that mediate memory representations. This has important implications for the elucidation and treatment of neurodegenerative diseases such as Alzheimer’s disease (AD). One important question in the context of preserving functional plasticity over the lifespan is the determination of the neurobiological structural and functional changes that contribute to the formation of memory during the juvenile time frame that might provide protection against later memory dysfunction by promoting the establishment of redundant neural pathways. The main question being, if memory formation during the juvenile period does strengthen and preserve memory stability over the lifespan, what are the neurobiological structural or functional substrates that mediate this effect? One neural attribute whose function may be altered with early life experience and provide a mechanism to preserve memory through the lifespan is glucose transport-linked calcium (Ca2+) buffering. Because peak increases in glucose utilization overlap with a timeframe during which spatial training can enhance later memory processing, it might be the case that learning-associated changes in glucose utilization would provide an important neural functional change to preserve memory function throughout the lifespan. The glucose transporters are proteins that are reduced in AD pathology and there is evidence that glucose reductions can impair Ca2+ buffering. In the absence of an appropriate supply of ATP, provided via glucose transport and glycolysis, Ca2+ levels can rise leading

Altered hippocampal lipid profile following acute postnatal exposure to Di(2-Ethylhexyl) phthalate in rats

Slight changes in the abundance of certain lipid species in the brain may drastically alter normal neurodevelopment via membrane stability, cell signalling, and cell survival. Previous findings have demonstrated that postnatal exposure to di (2-ethylhexyl) phthalate (DEHP) disrupts normal axonal and neural development in the hippocampus. The goal of the current study was to determine whether postnatal exposure to DEHP alters the lipid profile in the hippocampus during postnatal development. Systemic treatment with 10 mg/kg DEHP during postnatal development led to elevated levels of phosphatidylcholine and sphingomyelin in the hippocampus of female rats. There was no effect of DEHP exposure on the overall abundance of phosphatidylcholine or sphingomyelin in male rats or of lysophosphatidylcholine in male or female rats. Individual analyses of each identified lipid species revealed 10 phosphatidylcholine and six sphingomyelin lipids in DEHP-treated females and a single lysophosphatidylcholine in DEHP-treated males with a two-fold or higher increase in relative abundance. Our results are congruent with previous work that found that postnatal exposure to DEHP had a near-selective detrimental effect on hippocampal development in males but not females. Together, results suggest a neuroprotective effect of these elevated lipid species in females

Intra-Accumbens Injection of a Dopamine Aptamer Abates MK-801-Induced Cognitive Dysfunction in a Model of Schizophrenia

Systemic administration of the noncompetitive NMDA-receptor antagonist, MK-801, has been proposed to model cognitive deficits similar to those seen in patients with schizophrenia. The present work investigated the ability of a dopamine-binding DNA aptamer to regulate these MK-801-induced cognitive deficits when injected into the nucleus accumbens. Rats were trained to bar press for chocolate pellet rewards then randomly assigned to receive an intra-accumbens injection of a DNA aptamer (200 nM; n = 7), tris buffer (n = 6) or a randomized DNA oligonucleotide (n = 7). Animals were then treated systemically with MK-801 (0.1 mg/kg) and tested for their ability to extinguish their bar pressing response. Two control groups were also included that did not receive MK-801. Data revealed that injection of Tris buffer or the random oligonucleotide sequence into the nucleus accumbens prior to treatment with MK-801 did not reduce the MK-801-induced extinction deficit. Animals continued to press at a high rate over the entire course of the extinction session. Injection of the dopamine aptamer reversed this MK-801-induced elevation in lever pressing to levels as seen in rats not treated with MK-801. Tests for activity showed that the aptamer did not impair locomotor activity. Results demonstrate the in vivo utility of DNA aptamers as tools to investigate neurobiological processes in preclinical animal models of mental health disease

Utility of the Hebb–Williams maze paradigm for translational research in Fragile X syndrome: A direct comparison of mice and humans

To generate meaningful information, translational research must employ paradigms that allow extrapolation from animal models to humans. However, few studies have evaluated translational paradigms on the basis of defined validation criteria. We outline three criteria for validating translational paradigms. We then evaluate the Hebb–Williams maze paradigm (Hebb and Williams, 1946; Rabinovitch and Rosvold, 1951) on the basis of these criteria using Fragile X syndrome (FXS) as model disease. We focuse