Adenosine signalling to astrocytes coordinates brain metabolism and function.

Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply1,2. Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism3,4, but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood5,6. Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors. Stimulation of A2B receptors recruits the canonical cyclic adenosine 3',5'-monophosphate-protein kinase A signalling pathway, leading to rapid activation of astrocyte glucose metabolism and the release of lactate, which supplements the extracellular pool of readily available energy substrates. Experimental mouse models involving conditional deletion of the gene encoding A2B receptors in astrocytes showed that adenosine-mediated metabolic signalling is essential for maintaining synaptic function, especially under conditions of high energy demand or reduced energy supply. Knockdown of A2B receptor expression in astrocytes led to a major reprogramming of brain energy metabolism, prevented synaptic plasticity in the hippocampus, severely impaired recognition memory and disrupted sleep. These data identify the adenosine A2B receptor as an astrocytic sensor of neuronal activity and show that cAMP signalling in astrocytes tunes brain energy metabolism to support its fundamental functions such as sleep and memory.

Up-regulating GABA transporter-3 in the zona incerta prevents surgery-induced memory impairment in mice.

Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions.

Mesenchymal stem cell-derived exosomes improve neurogenesis and cognitive function of mice with methamphetamine addiction: A novel treatment approach.

BACKGROUND: Methamphetamine (METH) is a psychostimulant substance with highly addictive and neurotoxic effects, but no ideal treatment option exists to improve METH-induced neurocognitive deficits. Recently, mesenchymal stem cells (MSCs)-derived exosomes have raised many hopes for treating neurodegenerative sequela of brain disorders. This study aimed to determine the therapeutic potential of MSCs-derived exosomes on cognitive function and neurogenesis of METH-addicted rodents. METHODS: Male BALB/c mice were subjected to chronic METH addiction, followed by intravenous administration of bone marrow MSCs-derived exosomes. Then, the spatial memory and recognition memory of animals were assessed by the Barnes maze and the novel object recognition test (NORT). The neurogenesis-related factors, including NeuN and DCX, and the expression of Iba-1, a microglial activation marker, were assessed in the hippocampus by immunofluorescence staining. Also, the expression of inflammatory cytokines, including TNF-α and NF-κB, were evaluated by western blotting. RESULTS: The results showed that BMSCs-exosomes improved the time spent in the target quadrant and correct-to-wrong relative time in the Barnes maze. Also, NORT's discrimination index (DI) and recognition index (RI) were improved following exosome therapy. Additionally, exosome therapy significantly increased the expression of NeuN and DCX in the hippocampus while decreasing the expression of inflammatory cytokines, including TNF-α and NF-κB. Besides, BMSC-exosomes down-regulated the expression of Iba-1. CONCLUSION: Our findings indicate that BMSC-exosomes mitigated METH-caused cognitive dysfunction by improving neurogenesis and inhibiting neuroinflammation in the hippocampus.

Effects of unilateral hippocampal surgical procedures needed for calcium imaging on mouse behavior and adult hippocampal neurogenesis.

Hippocampus is essential for episodic memory formation, lesion studies demonstrating its role especially in processing spatial and temporal information. Further, adult hippocampal neurogenesis (AHN) in the dentate gyrus (DG) has also been linked to learning. To study hippocampal neuronal activity during events like learning, in vivo calcium imaging has become increasingly popular. It relies on the use of adeno-associated viral (AAV) vectors, which seem to lead to a decrease in AHN when applied on the DG. More notably, imaging requires the implantation of a relatively large lens into the tissue. Here, we examined how injection of an AAV vector and implantation of a 1-mm-diameter lens into the dorsal DG routinely used to image calcium activity impact the behavior of adult male C57BL/6 mice. To this aim, we conducted open-field, object-recognition and object-location tasks at baseline, after AAV vector injection, and after lens implantation. Finally, we determined AHN from hippocampal slices using a doublecortin-antibody. According to our results, the operations needed for in vivo imaging of the dorsal DG did not have adverse effects on behavior, although we noticed a decrease in AHN ipsilaterally to the operations. Thus, our results suggest that in vivo imaging can be safely used to, for example, correlate patterns of calcium activity with learned behavior. One should still keep in mind that the defects on the operated side might be functionally compensated by the (hippocampus in the) contralateral hemisphere.

Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction.

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular populations in the cortex and hippocampus, as well as in VAT, during the chronic phase after combined TBI-HFD showed amplification of central and peripheral microglia/macrophage responses, including superadditive changes in selected gene expression signatures and pathways. Furthermore, combined TBI and HFD caused additive dysfunction in Y-Maze, Novel Object Recognition (NOR), and Morris water maze (MWM) cognitive function tests. These novel data suggest that HFD-induced obesity and TBI can independently prime and support the development of altered states in brain microglia and VAT, including the disease-associated microglia/macrophage (DAM) phenotype observed in neurodegenerative disorders. The interaction between HFD and TBI promotes a shift toward chronic reactive microglia/macrophage transcriptomic signatures and associated pro-inflammatory disease-altered states that may, in part, underlie the exacerbation of cognitive deficits. Thus, targeting of HFD-induced reactive cellular phenotypes, including in peripheral adipose tissue immune cell populations, may serve to reduce microglial maladaptive states after TBI, attenuating post-traumatic neurodegeneration and neurological dysfunction.

Mouse hippocampal CA1 VIP interneurons detect novelty in the environment and support recognition memory.

In the CA1 hippocampus, vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) play a prominent role in disinhibitory circuit motifs. However, the specific behavioral conditions that lead to circuit disinhibition remain uncertain. To investigate the behavioral relevance of VIP-IN activity, we employed wireless technologies allowing us to monitor and manipulate their function in freely behaving mice. Our findings reveal that, during spatial exploration in new environments, VIP-INs in the CA1 hippocampal region become highly active, facilitating the rapid encoding of novel spatial information. Remarkably, both VIP-INs and pyramidal neurons (PNs) exhibit increased activity when encountering novel changes in the environment, including context- and object-related alterations. Concurrently, somatostatin- and parvalbumin-expressing inhibitory populations show an inverse relationship with VIP-IN and PN activity, revealing circuit disinhibition that occurs on a timescale of seconds. Thus, VIP-IN-mediated disinhibition may constitute a crucial element in the rapid encoding of novelty and the acquisition of recognition memory.

Role of dopamine neurons in familiarity.

Dopamine neurons signal the salience of environmental stimuli and influence learning, although it is less clear if these neurons also determine the salience of memories. Ventral tegmental area (VTA) dopamine neurons increase their firing in the presence of new objects and reduce it upon repeated, inconsequential exposures, marking the shift from novelty to familiarity. This study investigates how dopamine neuron activity during repeated familiar object exposure affects an animal's preference for new objects in a subsequent novel object recognition (NOR) test. We hypothesize that a single familiarization session will not sufficiently lower dopamine activity, such that the memory of a familiar object remains salient, leading to equal exploration of familiar and novel objects and weaker NOR discrimination. In contrast, multiple familiarization sessions likely suppress dopamine activity more effectively, reducing the salience of the familiar object and enhancing subsequent novelty discrimination. Our experiments in mice indicated that multiple familiarization sessions reduce VTA dopamine neuron activation, as measured by c-Fos expression, and enhance novelty discrimination compared with a single familiarization session. Dopamine neurons that show responsiveness to novelty were primarily located in the paranigral nucleus of the VTA and expressed vesicular glutamate transporter 2 transcripts, marking them as dopamine-glutamate neurons. Chemogenetic inhibition of dopamine neurons during a single session paralleled the effects of multiple sessions, improving NOR. These findings suggest that a critical role of dopamine neurons during the transition from novelty to familiarity is to modulate the salience of an object's memory.

Role of neuroestrogens in the regulation of social behaviors - From social recognition to mating.

In this mini-review, we summarize the brain distribution of aromatase, the enzyme catalyzing the synthesis of estrogens from androgens, and the mechanisms responsible for regulating estrogen production within the brain. Understanding this local synthesis of estrogens by neurons is pivotal as it profoundly influences various facets of social behavior. Neuroestrogen action spans from the initial processing of socially pertinent sensory cues to integrating this information with an individual's internal state, ultimately resulting in the manifestation of either pro-affiliative or - aggressive behaviors. We focus here in particular on aggressive and sexual behavior as the result of correct individual recognition of intruders and potential mates. The data summarized in this review clearly point out the crucial role of locally synthesized estrogens in facilitating rapid adaptation to the social environment in rodents and birds of both sexes. These observations not only shed light on the evolutionary significance but also indicate the potential implications of these findings in the realm of human health, suggesting a compelling avenue for further investigation.

The central role of the left inferior longitudinal fasciculus in the face-name retrieval network.

Unsuccessful retrieval of proper names (PNs) is commonly observed in patients suffering from neurological conditions such as stroke or epilepsy. While a large body of works has suggested that PN retrieval relies on a cortical network centered on the left anterior temporal lobe (ATL), much less is known about the white matter connections underpinning this process. Sparse studies provided evidence for a possible role of the uncinate fasciculus, but the inferior longitudinal fasciculus (ILF) might also contribute, since it mainly projects into the ATL, interconnects it with the posterior lexical interface and is engaged in common name (CN) retrieval. To ascertain this hypothesis, we assessed 58 patients having undergone a neurosurgery for a left low-grade glioma by means of a famous face naming (FFN) task. The behavioural data were processed following a multilevel lesion approach, including location-based analyses, voxel-based lesion-symptom mapping (VLSM) and disconnection-symptom mapping. Different statistical models were generated to control for sociodemographic data, familiarity, biographical knowledge and control cognitive performances (i.e., semantic and episodic memory and CN retrieval). Overall, VLSM analyses indicated that damage to the mid-to-anterior part of the ventro-basal temporal cortex was especially associated with PN retrieval deficits. As expected, tract-oriented analyses showed that the left ILF was the most strongly associated pathway. Our results provide evidence for the pivotal role of the ILF in the PN retrieval network. This novel finding paves the way for a better understanding of the pathophysiological bases underlying PN retrieval difficulties in the various neurological conditions marked by white matter abnormalities.

Electrocorticography reveals the dynamics of famous voice responses in human fusiform gyrus.

Voice and face processing occur through convergent neural systems that facilitate speaker recognition. Neuroimaging studies suggest that familiar voice processing engages early visual cortex, including the bilateral fusiform gyrus (FG) on the basal temporal lobe. However, what role the FG plays in voice processing and whether it is driven by bottom-up or top-down mechanisms is unresolved. In this study we directly examined neural responses to famous voices and faces in human FG with direct cortical surface recordings (electrocorticography) in epilepsy surgery patients. We tested the hypothesis that neural populations in human FG respond to famous voices and investigated the temporal properties of voice responses in FG. Recordings were acquired from five adult participants during a person identification task using visual and auditory stimuli from famous speakers (U.S. Presidents Barack Obama, George W. Bush, and Bill Clinton). Patients were presented with images of presidents or clips of their voices and asked to identify the portrait/speaker. Our results demonstrate that a subset of face-responsive sites in and near FG also exhibit voice responses that are both lower in magnitude and delayed (300-600 ms) compared with visual responses. The dynamics of voice processing revealed by direct cortical recordings suggests a top-down feedback-mediated response to famous voices in FG that may facilitate speaker identification.NEW & NOTEWORTHY Interactions between auditory and visual cortices play an important role in person identification, but the dynamics of these interactions remain poorly understood. We performed direct brain recordings of fusiform face cortex in human epilepsy patients performing a famous voice naming task, revealing the dynamics of famous voice processing in human fusiform face cortex. The findings support a model of top-down interactions from auditory to visual cortex to facilitate famous voice recognition.

The Onset of Maternal Behavior in Sheep and Goats: Endocrine, Sensory, Neural, and Experiential Mechanisms.

In sheep and goats, the onset of maternal behavior at parturition is characterized by a first phase called maternal responsiveness during which the mother is attracted to any newborn. In a second phase, called maternal selectivity, the mother establishes a selective bond with her young so that she only accepts it at suckling. After a description of the behavioral expression of both phases, this chapter reviews the physiological, sensory, and neural mechanisms involved. These two behavioral processes are synchronized with parturition by the vaginocervical stimulation induced by the expulsion of the newborn. Olfactory cues provided by the neonate are involved in maternal responsiveness and selectivity. Oxytocin supported by estrogens is the key factor for maternal responsiveness. The neural network involved in maternal responsiveness is mainly hypothalamic and is different from the circuitry involved in selectivity, which mainly concerns olfactory processing regions. Visual and auditory cues are necessary for offspring recognition at a distance. This multisensory recognition suggests that mothers form a mental image of their young. Maternal experience renders mothers more responsive to maternally relevant physiology and to young-related sensory inputs.

Musical emotions affect memory for emotional pictures.

Music is widely known for its ability to evoke emotions. However, assessing specific music-evoked emotions other than through verbal self-reports has proven difficult. In the present study, we explored whether mood-congruency effects could be used as indirect measures of specific music-evoked emotions. First, participants listened to 15 music excerpts chosen to induce different emotions; after each excerpt, they were required to look at four different pictures. The pictures could either: (1) convey an emotion congruent with that conveyed by the music (i.e., congruent pictures); (2) convey a different emotion than that of the music, or convey no emotion (i.e., incongruent pictures). Second, participants completed a recognition task that included new pictures as well as already seen congruent and incongruent pictures. From previous findings about mood-congruency effects, we hypothesized that if music evokes a given emotion, this would facilitate memorization of pictures that convey the same emotion. Results revealed that accuracy in the recognition task was indeed higher for emotionally congruent pictures than for emotionally incongruent ones. The results suggest that music-evoked emotions have an influence on subsequent cognitive processing of emotional stimuli, suggesting a role of mood-congruency based recall tasks as non-verbal methods for the identification of specific music-evoked emotions.

Social factors and the neurobiology of pathogen avoidance.

Although the evolutionary causes and consequences of pathogen avoidance have been gaining increasing interest, there has been less attention paid to the proximate neurobiological mechanisms. Animals gauge the infection status of conspecifics and the threat they represent on the basis of various sensory and social cues. Here, we consider the neurobiology of pathogen detection and avoidance from a cognitive, motivational and affective state (disgust) perspective, focusing on the mechanisms associated with activating and directing parasite/pathogen avoidance. Drawing upon studies with laboratory rodents, we briefly discuss aspects of (i) olfactory-mediated recognition and avoidance of infected conspecifics; (ii) relationships between pathogen avoidance and various social factors (e.g. social vigilance, social distancing (approach/avoidance), social salience and social reward); (iii) the roles of various brain regions (in particular the amygdala and insular cortex) and neuromodulators (neurotransmitters, neuropeptides, steroidal hormones and immune components) in the regulation of pathogen avoidance. We propose that understanding the proximate neurobiological mechanisms can provide insights into the ecological and evolutionary consequences of the non-consumptive effects of pathogens and how, when and why females and males engage in pathogen avoidance.

Timing of iron deficiency and recognition memory in infancy.

Objective: To determine the relationship between iron deficiency (or iron-deficient, ID) and neural correlates of recognition memory depending on ID timing (gestation vs. infancy) and infant age at testing (9 vs. 18 months).Study design: Event-related potentials (ERP) were used in a visual recognition memory task (mother vs. stranger face) to compare healthy term infants according to iron status at birth and 9 months. Fetal-neonatal ID was defined as cord serum ferritin < 75 µg/l or zinc protoporphrin/heme ratio > 118 µmol/mol, postnatal ID as ≥ 2 abnormal iron measures at 9 months with normal cord-blood iron status, and iron-sufficient as not ID at birth or 9 months. Recognition of mother faces was measured by negative component (Nc) and late slow wave (LSW). These ERP components reflect attention and memory updating processes, respectively.Results: All groups showed differences in Nc amplitude elicited by mother and stranger faces at 9 months. At 18 months, only postnatal ID and iron-sufficient groups showed condition differences in Nc amplitude. However, the 2 groups were different in the involved brain regions. For LSW, only the 2 ID groups showed condition differences in amplitude at 9 months. At 18 months, condition differences were not observed in any group.Conclusions: This study indicates that the timing of ID in early life (fetal-neonatal vs. postnatal) modulates the impact of ID on recognition memory. Such impact also varies depending on the age of infants at testing (9 vs. 18 months).

Autonomic factors do not underlie the elevated self-disgust levels in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is manifested along with non-motor symptoms such as impairments in basic emotion regulation, recognition and expression. Yet, self-conscious emotion (SCEs) such as self-disgust, guilt and shame are under-investigated. Our previous research indicated that Parkinson patients have elevated levels of self-reported and induced self-disgust. However, the cause of that elevation-whether lower level biophysiological factors, or higher level cognitive factors, is unknown. METHODS: To explore the former, we analysed Skin Conductance Response (SCR, measuring sympathetic activity) amplitude and high frequency Heart Rate Variability (HRV, measuring parasympathetic activity) across two emotion induction paradigms, one involving narrations of personal experiences of self-disgust, shame and guilt, and one targeting self-disgust selectively via images of the self. Both paradigms had a neutral condition. RESULTS: Photo paradigm elicited significant changes in physiological responses in patients relative to controls-higher percentages of HRV in the high frequency range but lower SCR amplitudes, with patients to present lower responses compared to controls. In the narration paradigm, only guilt condition elicited significant SCR differences between groups. CONCLUSIONS: Consequently, lower level biophysiological factors are unlikely to cause elevated self-disgust levels in Parkinson's disease, which by implication suggests that higher level cognitive factors may be responsible.

The G protein-coupled estrogen receptor (GPER) regulates recognition and aversively-motivated memory in male rats.

Estrogens, particularly 17ß-estradiol (estradiol, E2), regulate memory formation. E2 acts through its intracellular receptors, estrogen receptors (ER) ERα and ERß, as well as a recently identified G protein-coupled estrogen receptor (GPER). Although the effects of E2 on memory have been investigated, studies examining the effects of GPER stimulation are scarce. Selective GPER agonism improves memory in ovariectomized female rats, but little information is available regarding the effects of GPER stimulation in male rodents. The aim of the present study was to investigate the effects of the GPER agonist, G1, on consolidation and reconsolidation of inhibitory avoidance (IA) and object recognition (OR) memory in male rats. Animals received vehicle, G1 (15, 75, 150 µg/kg; i.p.), or the GPER antagonist G15 (100 µg/kg; i.p.) immediately after training, or G1 (150 µg/kg; i.p.) 3 or 6 h after training. To investigate reconsolidation, G1 was administered immediately after IA retention Test 1. Results indicated that G1 administered immediately after training at the highest dose enhanced both OR and IA memory consolidation, while GPER blockade immediately after training impaired OR. No effects of GPER stimulation were observed when G1 was given 3 or 6 h after training or after Test 1. The present findings provide evidence that GPER is involved in the early stages of memory consolidation in both neutral and emotional memory tasks in male adult rats.

Social cognition in individuals born preterm.

Faces hold a substantial value for effective social interactions and sharing. Covering faces with masks, due to COVID-19 regulations, may lead to difficulties in using social signals, in particular, in individuals with neurodevelopmental conditions. Daily-life social participation of individuals who were born preterm is of immense importance for their quality of life. Here we examined face tuning in individuals (aged 12.79 ± 1.89 years) who were born preterm and exhibited signs of periventricular leukomalacia (PVL), a dominant form of brain injury in preterm birth survivors. For assessing the face sensitivity in this population, we implemented a recently developed experimental tool, a set of Face-n-Food images bordering on the style of Giuseppe Arcimboldo. The key benefit of these images is that single components do not trigger face processing. Although a coarse face schema is thought to be hardwired in the brain, former preterms exhibit substantial shortages in the face tuning not only compared with typically developing controls but also with individuals with autistic spectrum disorders. The lack of correlations between the face sensitivity and other cognitive abilities indicates that these deficits are domain-specific. This underscores impact of preterm birth sequelae for social functioning at large. Comparison of the findings with data in individuals with other neurodevelopmental and neuropsychiatric conditions provides novel insights into the origins of deficient face processing.

Pituitary Adenylate Cyclase-Activating Polypeptide Protects Against Cognitive Impairment Caused by Chronic Cerebral Hypoperfusion.

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) has beneficial effects in learning and memory. However, the mechanism by which PACAP improves cognitive impairment of vascular dementia (VaD) is not clear. METHODS: We established a VaD model by bilateral common carotid stenosis (BCAS) to investigate the molecular mechanism of cognitive impairment. Protein levels of PACAP, Sirtuin 3 (Sirt3), brain-derived neurotrophic factor (BDNF), and postsynaptic density 95 (PSD-95) were assessed by Western blot. In vitro, oxygen glucose deprivation (OGD) was used to simulate the ischemia/hypoxia state. HT22 cells were transfected with Sirt3 knockdown and overexpression to study the relationship between PACAP, Sirt3, and BDNF. In vivo, PACAP was administered intranasally to assess its protective effects on BCAS. RESULTS: The study showed that the levels of PACAP, Sirt3, BDNF, and PSD-95 were decreased in the BCAS model of VaD. PACAP increased the protein levels of Sirt3, BDNF, PSD-95, Bcl-2, and Bax under OGD condition in vitro. Sirt3 regulated BDNF and synaptic plasticity. Intranasal PACAP increased the protein levels of PAC1, Sirt3, BDNF, and PSD-95 in vivo. CONCLUSIONS: This study provides evidence that PACAP regulates synaptic plasticity and plays an antiapoptotic role through Sirt3.

Aging-Related Neural Disruption Might Predispose to Postoperative Cognitive Impairment Following Surgical Trauma.

BACKGROUND: Accumulating evidence has demonstrated that aging is associated with an exaggerated response to surgical trauma together with cognitive impairments. This has significant implications for the development of clinical phenotype such as perioperative neurocognitive disorders (PND), which is a common complication following surgery, especially for the elderly. However, the mechanism by which aging brain is vulnerable to surgical trauma remains to be elucidated. OBJECTIVE: To test whether age-related alterations in hippocampal network activities contribute to increased risk of PND following surgery. METHODS: Thirty-two adult and seventy-two aged male C57BL/6 mice undergone sevoflurane anesthesia and exploratory laparotomy were used to mimic human abdominal surgery. For the interventional study, mice were treated with minocycline. Behavioral tests were performed post-surgery with open field, novel object recognition and fear conditioning tests, respectively. The brain tissues were then harvested and subjected to biochemistry studies. Local field potential (LFP) recording was performed in another separate experiment. RESULTS: Aged mice displayed signs of neuroinflammation, as reflected by significantly increased proinflammatory mediators in the hippocampus. Also, aged mice displayed persistently decreased oscillation activities under different conditions, both before and after surgery. Further correlation analysis suggested that theta power was positively associated with time with novel object, while γ oscillation activity was positively associated with freezing time to context. Of note, downregulation of neuroinflammation by microglia inhibitor minocycline reversed some of these abnormities. CONCLUSION: Our study highlights that age-related hippocampal oscillation dysregulation increases the risk of PND incidence, which might provide diagnostic/prognostic biomarkers for PND and possible other neurodegenerative diseases.

Perirhinal cortex and the recognition of relative familiarity.

Spontaneous object recognition (SOR) is a widely used task of recognition memory in rodents which relies on their propensity to explore novel (or relatively novel) objects. Network models typically define perirhinal cortex as a region required for recognition of previously seen objects largely based on findings that lesions or inactivations of this area produce SOR deficits. However, relatively little is understood about the relationship between the activity of cells in the perirhinal cortex that signal novelty and familiarity and the behavioural responses of animals in the SOR task. Previous studies have used objects that are either highly familiar or absolutely novel, but everyday memory is for objects that sit on a spectrum of familiarity which includes objects that have been seen only a few times, or objects that are similar to objects which have been previously experienced. We present two studies that explore cellular activity (through c-fos imaging) within perirhinal cortex of rats performing SOR where the familiarity of objects has been manipulated. Despite robust recognition memory performance, we show no significant changes in perirhinal activity related to the level of familiarity of the objects. Reasons for this lack of familiarity-related modulation in perirhinal cortex activity are discussed. The current findings support emerging evidence that perirhinal responses to novelty are complex and that task demands are critical to the involvement of perirhinal cortex in the control of object recognition memory.