Nonspatial Working Memory Research Articles

Interaction between visual working memory and upright postural control in young adults: an event-related potential study based on the n-back paradigm.

As a part of the overall information-processing system of the brain, postural control is related to the cognitive processes of working memory. Previous studies have suggested that cognitive tasks and postural control processes can compete for resources in common brain areas, although there is an "inverted U" relationship between arousal level and behavioral control - the arousal level of individuals changes when performing cognitive tasks. However, the exact neural connections between the two are unclear. This may be related to the nature of cognitive tasks. Some studies believe that posture occupies not only spatial information processing resources but also visual non-spatial information processing resources. Other studies believe that posture control only occupies spatial information processing resources in the central system, but does not occupy non-spatial information processing resources. Previous studies used different cognitive task materials and reached different conclusions. In this study, we used the same visuospatial and non-spatial materials, the n-back visual working memory paradigm, the event-related potential technique to investigate the effects of visuospatial and non-spatial working memory tasks on adolescents' postural control under different cognitive loads. The results of this study showed that in both visuospatial and non-spatial conditions, the N1 effect of the parieto-occipital lobe was larger during upright posture than in the sitting position (160-180 ms), the P300 effect of the central parieto-occipital region (280-460 ms) was induced by working memory in different postures, and the P300 wave amplitude was higher in the sitting position than in the upright position. We demonstrated that upright postural control enhances early selective attention but interferes with central memory encoding, thus confirming that postural control and visuospatial and non-spatial working memory share brain regions and compete with each other.

Nucleus accumbens core dopamine D2 receptors are required for performance of the odor span task in male rats.

The nucleus accumbens (NAc) core gates motivationally relevant behavioral action sequences through afferents from cortical and subcortical brain regions. While the role of the NAc core in reward and effort-based decision making is well established, its role in working memory (WM) processes is incompletely understood. The odor span task (OST) has been proposed as a measure of non-spatial working memory capacity (WMC) as it requires rodents to select a novel odor from an increasing number of familiar odors to obtain a food reward. To assess the role of the NAc core in the OST using (1) reversible chemical inactivation and (2) selective blockade of dopamine D1 and D2 receptors in the area. Well-trained male rats were tested on the OST following intra-NAc core infusions of muscimol/baclofen, the D1 receptorantagonist SCH-23390 (1 μg/hemisphere) and the D2 receptorantagonist eticlopride (1 μg/hemisphere). Behavioral measurements included the average odor span, maximum odor span, choice latency, searching vigor, and patterns of responding during foraging that may relate to impulsivity. Chemical inactivation of the NAc core significantly decreased odor span relative to sham and vehicle conditions. Selective antagonism of D2, but not D1, receptors in the NAc core also produced deficits in odor span. We found that secondary behavioral measures of choice latency, searching vigor, and responding to the first odor stimulus encountered were largely unaffected by treatment. These findings suggest that D2 receptors in the NAc core are required for OST performance.

Effect of Sevoflurane and Isoflurane on Post-Anaesthesia Cognitive Dysfunction in Normal and Type II Diabetic Rats.

Both animal and human studies have documented cognitive and behavioural impairment after exposure to inhalational anaesthetics. Therefore, the current study was designed to demonstrate if the anaesthetics isoflurane and Sevoflurane can result in postoperative cognition dysfunction in normal and diabetic rats. Sixty male Wister rats aged 12 weeks were divided into 6 groups (n=10); group C (standard control), group CD (diabetic control), group S (sevoflurane anaesthesia), group I (isoflurane anaesthesia), group SD (diabetic sevoflurane anaesthesia) group ID (diabetic isoflurane anaesthesia). Animals were anaesthetized with either 2. 5% sevoflurane or 1.5% isoflurane, respectively, for 2h. 1 week later, animals were undergone cognitive tests in (a Morris water maze, T maze and open field arena), the animals were sacrificed, and hippocampus homogenates were studied for caspase 3 activity by western blot assay. Induction of type II diabetes in CD, SD and ID groups was carried out by feeding on a high-fat diet for 8 weeks before the start of the experiment. During the fourth week, Type II diabetes was induced in the experimental group by a single IP injection of 30 mg/kg STZ. Control (normal and diabetic) rats showed no change in long-term/reference memory, non-spatial working memory, exploratory activity or caspase 3 expression in the hippocampus homogenate. Anaesthesia with isoflurane in normoglycemic rats resulted in a significant decline in long-term/reference memory and non-spatial working memory, while exploratory activity and caspase 3 expressions in hippocampus homogenate showed no change to normal control rats. Both isoflurane and Sevoflurane in diabetic rats demonstrated a decline in long-term/reference memory, non-spatial working memory, exploratory activity and caspase 3 expression in hippocampus homogenate compared with normal control rats. Diabetes revealed significant post-anaesthesia cognitive dysfunction after anaesthesia with Sevoflurane or isoflurane in all the studied domains compared to standard control or diabetic control.

Enriched Housing Rehabilitation for Stroke Recovery in Spontaneously Hypertensive Rats

Long‐term disability due to stroke is a major global health burden, and there is an urgent need for interventions targeting the post‐acute phase of stroke to improve motor and cognitive deficits. Hypertension is a major contributor to overall risk for stroke and is associated with worse functional outcomes and mortality. Previous studies from our laboratory suggest that the spontaneously hypertensive rat (SHR) model of experimental hypertension develops profound, progressive post‐stroke cognitive impairment. Enriched housing (EH) conditions have shown promise as a rehabilitation strategy to enhance brain plasticity and improve behavior in preclinical studies using relatively young, healthy, adult male animals. However, the impact of hypertension on stroke recovery outcomes in response to EH remains unknown. The goal of this study was to test EH conditions for stroke rehabilitation in an established preclinical model of hypertension. We hypothesized that EH would improve the sensorimotor and cognitive recovery response to stroke in male SHRs compared to standard housing (SH) conditions. SHRs (aged 17w) were subjected to either sham or 60‐min. middle cerebral artery occlusion (MCAO) surgery to induce stroke. Stroke severity was controlled for using the following inclusion criteria: adhesive removal time (ART) > 35 sec. and either a modified Bederson score <= 6 or weight loss > 10%). Animals were then randomized to EH or SH conditions. EH conditions consisted of a novel environment to promote exercise and social interaction and was implemented for 2 hrs/day, 5 days/week for 4w starting 1w after surgery. Blood pressure was monitored by tail‐cuff plethysmography at baseline, 1, 3, and 7w post‐surgery. Animals were followed for an additional 4w after rehabilitation intervention for behavioral outcome measures. Motor recovery was assessed using ART (Figure 1), and novel object recognition (NOR, Figure 2) and 2‐trial Y‐maze were used to determine cognitive recovery. Stroked animals had significantly increased adhesive removal times at 3d and 6w post‐MCAO compared to sham animals, but EH conditions did not significantly impact this sensorimotor deficit. Stroke+EH animals had a significant decrease from their pre‐stroke recognition indices 1w post‐stroke compared to Sham+EH animals, suggesting there may have been some acute deficits in non‐spatial working memory. There were no significant differences among groups in time spent in the novel arm of the 2‐trial y‐maze, suggesting that stroke did not alter spatial working memory. Overall, these findings suggest that there are significant sensorimotor deficits post‐stroke, and the mild improvement in ART over time in stroked hypertensive animals occurs independently of EH. Cognitive deficits were similar in stroke and sham animals, regardless of rehabilitation, except for 1w post‐stroke, which is likely before EH would have had a significant impact on non‐spatial working memory. However, this effect might be skewed by a significant increase in NOR exploration time in Sham+EH animals. Unlike in previous studies in our laboratory, 60‐min. MCAO did not appear to induce significant post‐stroke cognitive impairment in these hypertensive animals compared to sham procedure.

Abstract WMP117: Effects Of Chronic Remote Ischemic Conditioning In A VCID Mouse Appears RBCNOS3 Dependent

Background and Purpose: Chronic remote ischemic conditioning (C-RIC) is effective at improving cerebral blood flow (CBF) inducing vascular remodeling, and improving cognition in a bilateral carotid artery stenosis (BCAS) mouse model, a model for Vascular Cognitive Impairment and Dementia (VCID). This augmentation is associated with increases of plasma nitrite. Our aim was to determine if the beneficial effect of C-RIC was red blood cell (NOS3) dependent. Methods: Microcoil (01.8 mm) induced BCAS model was used to induce chronic hypoperfusion. Aged RBCNOS3-KO and its control groups, NOS3flox-flox male mice (>12 months ) were randomly assigned to Sham RIC and RIC of both strains. RIC was started 7d post-surgery daily for 4 weeks. Behavioral test and CBF was performed before termination. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for motor/muscular impairment. Histopathological staining was also assessed of the brain tissues. Results: C-RIC-therapy for 4 weeks did not improve CBF in the RBCNOS3KO groups at 4 th weeks compared to ShamRIC groups. However, C-RIC therapy for 4 weeks significantly improved CBF in NOS3flox-flox groups compared to ShamRIC groups. Similarly, there was no significant change in the RBCNOS3 KO mice between the ShamRIC and RIC groups in the discrimination index/exploration time as determined by the NOR test or poor motor function as determined by hanging wire and beam walk test whereas the NOS3flox-flox mice did show improved cognition with RIC. Conclusions: The beneficial effect of C-RIC in the BCAS model is abrogated in RBCNOS3 KO mice indicating that the effect of C-RIC is NOS3 dependent.

Behavioral and Neuroanatomical Consequences of Cell-Type Specific Loss of Dopamine D2 Receptors in the Mouse Cerebral Cortex

Developmental dysregulation of dopamine D2 receptors (D2Rs) alters neuronal migration, differentiation, and behavior and contributes to the psychopathology of neurological and psychiatric disorders. The current study is aimed at identifying how cell-specific loss of D2Rs in the cerebral cortex may impact neurobehavioral and cellular development, in order to better understand the roles of this receptor in cortical circuit formation and brain disorders. We deleted D2R from developing cortical GABAergic interneurons (Nkx2.1-Cre) or from developing telencephalic glutamatergic neurons (Emx1-Cre). Conditional knockouts (cKO) from both lines, Drd2fl/fl, Nkx2.1-Cre+ (referred to as GABA-D2R-cKO mice) or Drd2fl/fl, Emx1-Cre+ (referred to as Glu-D2R-cKO mice), exhibited no differences in simple tests of anxiety-related or depression-related behaviors, or spatial or nonspatial working memory. Both GABA-D2R-cKO and Glu-D2R-cKO mice also had normal basal locomotor activity, but GABA-D2R-cKO mice expressed blunted locomotor responses to the psychotomimetic drug MK-801. GABA-D2R-cKO mice exhibited improved motor coordination on a rotarod whereas Glu-D2R-cKO mice were normal. GABA-D2R-cKO mice also exhibited spatial learning deficits without changes in reversal learning on a Barnes maze. At the cellular level, we observed an increase in PV+ cells in the frontal cortex of GABA-D2R-cKO mice and no noticeable changes in Glu-D2R-cKO mice. These data point toward unique and distinct roles for D2Rs within excitatory and inhibitory neurons in the regulation of behavior and interneuron development, and suggest that location-biased D2R pharmacology may be clinically advantageous to achieve higher efficacy and help avoid unwanted effects.

Ocimum sanctum Linn. Extract Improves Cognitive Deficits in Olfactory Bulbectomized Mice via the Enhancement of Central Cholinergic Systems and VEGF Expression.

This study aimed to clarify the antidementia effects of ethanolic extract of Ocimum sanctum Linn. (OS) and its underlying mechanisms using olfactory bulbectomized (OBX) mice. OBX mice were treated daily with OS or a reference drug, donepezil (DNP). Spatial and nonspatial working memory performance was measured using a modified Y maze test and a novel object recognition test, respectively. Brain tissues of the animals were subjected to histochemical and neurochemical analysis. OS treatment attenuated OBX-induced impairment of spatial and nonspatial working memories. OBX induced degeneration of septal cholinergic neurons, enlargement of the lateral ventricles, and suppression of hippocampal neurogenesis. OS and DNP treatment also depressed these histological damages. OS administration reduced ex vivo activity of acetylcholinesterase in the brain. OBX diminished the expression levels of genes coding vascular endothelial growth factor (VEGF) and VEGF receptor type 2 (VEGFR2). Treatment with OS and DNP reversed OBX-induced decrease in VEGF gene and protein expression levels without affecting the expression of the VEGFR2 gene. These results demonstrate that the administration of OS can lessen the cognitive deficits and neurohistological damages of OBX and that these actions are, at least in part, mediated by the enhancement of central cholinergic systems and VEGF expression.

Brain hemodynamic response in Examiner\u2013Examinee dyads during spatial short-term memory task: an fNIRS study

The Corsi Block-Tapping test (CBT) is a measure of spatial working memory (WM) in clinical practice, requiring an examinee to reproduce sequences of cubes tapped by an examiner. CBT implies complementary behaviors in the examiners and the examinees, as they have to attend a precise turn taking. Previous studies demonstrated that the Prefrontal Cortex (PFC) is activated during CBT, but scarce evidence is available on the neural correlates of CBT in the real setting. We assessed PFC activity in dyads of examiner–examinee participants while completing the real version of CBT, during conditions of increasing and exceeding workload. This procedure allowed to investigate whether brain activity in the dyads is coordinated. Results in the examinees showed that PFC activity was higher when the workload approached or reached participants’ spatial WM span, and lower during workload conditions that were largely below or above their span. Interestingly, findings in the examiners paralleled the ones in the examinees, as examiners’ brain activity increased and decreased in a similar way as the examinees’ one. In the examiners, higher left-hemisphere activity was observed suggesting the likely activation of non-spatial WM processes. Data support a bell-shaped relationship between cognitive load and brain activity, and provide original insights on the cognitive processes activated in the examiner during CBT.

Behavioral and Neurochemical Effects of Extra Virgin Olive Oil Total Phenolic Content and Sideritis Extract in Female Mice

The aim of this study was to determine the cognitive and behavioral effects of extra virgin olive oil total phenolic content (TPC) and Sideritis (SID) extracts in female mice, and identify the associated neurochemical changes in the hippocampus and the prefrontal cortex. All animals received intraperitoneal low or high doses of TPC, SID or vehicle treatment for 7 days and were subjected to the Open Field (OF), Novel Object Recognition (NOR) and Tail Suspension Test (TST). The prefrontal cortex and hippocampus were dissected for analysis of neurotransmitters and aminoacids with high performance liquid chromatography with electrochemical detection (HPLC-ED). Both TPC doses enhanced vertical activity and center entries in the OF, which could indicate an anxiolytic-like effect. In addition, TPC enhanced non-spatial working memory and, in high doses, exerted antidepressant effects. On the other hand, high SID doses remarkably decreased the animals’ overall activity. Locomotor and exploratory activities were closely associated with cortical increases in serotonin turnover induced by both treatments. Cognitive performance was linked to glutamate level changes. Furthermore, TPC reduced cortical taurine levels, while SID reduced cortical aspartate levels. TPC seems to have promising cognitive, anxiolytic and antidepressant effects, whereas SID has sedative effects in high doses. Both extracts act in the brain, but their specific actions and properties merit further exploration.

Tracking spatial and non-spatial working memory representations coded in human oscillatory brain activity

Tracking spatial and non-spatial working memory representations coded in human oscillatory brain activity

Abstract WP480: Beneficial Effect of Chronic-Remote Ischemic Conditioning (C-RIC) is Dependent Upon Circulating Blood Cell NOS3 in a Vascular Cognitive Impairment and Dementia (VCID) Model

Background and Purpose: Chronic remote ischemic conditioning (C-RIC) is effective at improving cerebral blood flow (CBF) inducing vascular remodeling, and improving cognition in a bilateral carotid artery stenosis (BCAS) mouse model, a model for Vascular Cognitive Impairment and Dementia (VCID). This effect is lost in NOS3-KO mice. We wanted to determine if the beneficial effect of C-RIC can be restored by bone marrow cell-derived NOS3. Methods: We prepared BM chimera from adult WT (B6.SJL-Ptprc a ; CD45.1) to adult NOS3-KO (B6.129; CD45.2) & vice versa in male mice (5-6 months) following confirmation for BM engrafting with flow cytometry at 2 weeks. Microcoil (0.18 mm) induced BCAS model was used to induce chronic hypoperfusion. Mice were randomly assigned to 3-groups: (1) Sham (2) BCAS and (3) BCAS+RIC. RIC was started 7d post-surgery daily for 3-4 weeks. Behavioral test and CBF was performed before termination. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for motor/muscular impairment. We measured whole blood P-NOS3, P-AMPK and VEGFR2/CD31 by flow cytometry. Results: C-RIC-therapy for 3-4 weeks improves CBF in engrafted BM of WT into NOS3-KO in the BCAS+RIC groups at both 2 weeks and 4 weeks compared to BCAS (Sham RIC groups).No effect of C-RIC was shown in engrafted BM of NOS3 into WT. There was significant change between the BCAS and BCAS+RIC groups in the functional outcomes and histopathological evidences also reflects major changing in the groups in the BM of WT into NOS3-KO mice. Whole blood P-NOS3, P-AMPK and VEGFR2/CD31 was increased by C-RIC. However, no effect was shown in the NOS3-KO into WT chimera. Conclusions: The Beneficial effect of C-RIC is dependent upon bone marrow derived NOS3.Further studies are needed to determine if the red blood cell is the key cell carrying NOS3

Aryl hydrocarbon receptor modulates stroke-induced astrogliosis and neurogenesis in the adult mouse brain

BackgroundThe aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor activated by environmental agonists and dietary tryptophan metabolites for the immune response and cell cycle regulation. Emerging evidence suggests that AHR activation after acute stroke may play a role in brain ischemic injury. However, whether AHR activation alters poststroke astrogliosis and neurogenesis remains unknown.MethodsWe adopted conditional knockout of AHR from nestin-expressing neural stem/progenitor cells (AHRcKO) and wild-type (WT) mice in the permanent middle cerebral artery occlusion (MCAO) model. WT mice were treated with either vehicle or the AHR antagonist 6,2′,4′-trimethoxyflavone (TMF, 5 mg/kg/day) intraperitoneally. The animals were examined at 2 and 7 days after MCAO.ResultsThe AHR signaling pathway was significantly upregulated after stroke. Both TMF-treated WT and AHRcKO mice showed significantly decreased infarct volume, improved sensorimotor, and nonspatial working memory functions compared with their respective controls. AHR immunoreactivities were increased predominantly in activated microglia and astrocytes after MCAO compared with the normal WT controls. The TMF-treated WT and AHRcKO mice demonstrated significant amelioration of astrogliosis and microgliosis. Interestingly, these mice also showed augmentation of neural progenitor cell proliferation at the ipsilesional neurogenic subventricular zone (SVZ) and the hippocampal subgranular zone. At the peri-infarct cortex, the ipsilesional SVZ/striatum, and the hippocampus, both the TMF-treated and AHRcKO mice demonstrated downregulated IL-1β, IL-6, IFN-γ, CXCL1, and S100β, and concomitantly upregulated Neurogenin 2 and Neurogenin 1.ConclusionNeural cell-specific AHR activation following acute ischemic stroke increased astrogliosis and suppressed neurogenesis in adult mice. AHR inhibition in acute stroke may potentially benefit functional outcomes likely through reducing proinflammatory gliosis and preserving neurogenesis.

The nature of top-down signals during non-spatial working memory

The nature of top-down signals during non-spatial working memory

Stimulus-driven attention and cognitive control during encoding: An event related brain potentials study

Stimulus-driven attention drawn to relevant items can improve working memory (WM) whether attentional capture is driven by salient, low level features or by contingent salience from shared features with targets. In the current work, we examined the time course of enhanced attention to contingently salient information in a non-spatial WM task using event related brain potentials (ERPs). In line with previous work, we predicted that the encoding of contingently salient stimuli would be associated with an enhancement of cognitive control processes rather than low-level salience detection. The results of this study supported this hypothesis, evidenced by a posterior P3 component of greater amplitude for contingently salient stimuli relative to stimuli of a control color, which is thought to reflect enhanced attention to information that matches a target held in WM. However, P3 amplitude during encoding was unrelated to subsequent memory accuracy. As an exploratory follow up on these results, we conducted a regression analysis including beliefs about ability to focus attention as a moderator, which interacted with P3 amplitude to predict WM recall of salient letters. Furthermore, source localization analyses implicated a significant contribution of regions in the salience network to the detection of target stimuli, but only frontal control regions showed a greater response to salient than control letters. Thus, the results of this experiment suggest that participants enhance cognitive control during the encoding of contingently salient stimuli, but that the relationship between this neural process during encoding and subsequent benefits to WM recall might depend on individual differences in attentional focus.

Persistent Alterations of Accumbal Cholinergic Interneurons and Cognitive Dysfunction after Adolescent Intermittent Ethanol Exposure

Adolescent binge drinking renders young drinkers vulnerable to alcohol use disorders in adulthood; therefore, understanding alcohol-induced brain damage and associated cognitive dysfunctions is of paramount importance. Here we investigated the effects of binge-like adolescent intermittent ethanol (AIE) exposure on nonspatial working memory, behavioral flexibility and cholinergic alterations in the nucleus accumbens (NAc) in male and female rats. On postnatal days P25–57 rats were intubated with water or ethanol (at a dose of 5 g/kg) on a 2-day-on/2-day-off cycle and were then tested in adulthood on social recognition and probabilistic reversal learning tasks. During the social recognition task AIE-treated rats spent similar amounts of time interacting with familiar and novel juveniles, indicating an impaired ability to sustain memory of the familiar juvenile. During probabilistic reversal learning, AIE-treated male and female rats showed behavioral inflexibility as indicated by a higher number of trials needed to complete three reversals within a session, longer response latencies for lever selection, and for males, a higher number of errors as compared to water-treated rats. AIE exposure also reduced the number of cholinergic interneurons in the NAc in males and females. These findings indicate AIE-related pathologies of accumbal cholinergic interneurons and long lasting cognitive-behavioral deficits, which may be associated with cortico-striatal hypofunction.

Abstract WP557: Chronic Remote Ischemic Conditioning (C-RIC) Induces Collateral Remodeling and Improves Functional Outcomes Independent of Sex in Aged Mouse Model of Vascular Cognitive Impairment and Dementia (VCID)

Background and Purpose: There is presently no specific therapy for the treatment of VCID. We reported that daily C-RIC (4mo) is effective in young mice by improving cerebral blood flow (CBF), minimizing white matter (WM) damage and improving functional outcomes in Bilateral Carotid Artery Stenosis model (BCAS.) The purpose of this study was to evaluate whether 4 months (4 MO-C-RIC) is effective in male and female aged mouse and if the treatment effects are durable out to 6MOS. Methods: Microcoil induced BCAS model was used to induce chronic hypoperfusion. Adult C57BL/6 both male & female mice (14-months ) were randomly assigned to 3-different groups (N=10), and subjected to Sham, BCAS+sham RIC, BCAS+RIC. C-RIC was started 7d post-surgery daily for 4MOs. Behavioral test and CBF was performed at 1, 4 and 6MO after BCAS and Sham surgery. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for motor/muscular impairment. Histopathology as well as immunohistochemistry for CD31/α-SMA; GFAP, myelin basic protein (MBP) and beta-amyloid were also performed on the brain tissue collected after the neurobehavioral tests. Results: C-RIC-therapy for 4MO significantly improved CBF in the male and female BCAS+C-RIC groups at all time points compared to BCAS-Sham RIC groups. Mice from the BCAS group +Sham C-RIC group showed significant loss in the discrimination index as determined by the NOR test, and poor motor function in hanging wire and beam walk test. C-RIC- significantly improved these functional outcomes. Histopathology showed prevention of WM degeneration and myelin basic protein by C-RIC. Immunohistochemical analysis at 6 MOs showed increased CD31 (angiogenesis) and a-SMA staining (arteriogenesis) indicating collateral remodeling in the C-RIC group compared to BCAS-sham RIC. Conclusions: Daily 4MO C-RIC-therapy improves long term CBF and vascular architecture at 6 MO and reduces WM damage and improves functional outcomes in aged males and females C-RIC induces durable long term collateral remodeling. C-RIC is a promising therapy for VCID and is ready for future clinical trials in VCID.

Abstract WP137: Angiotensin Type 2 Receptor Stimulation With Compound 21 Prevents Delayed Cognitive Impairment in Hypertensive, Ovariectomized Female Rats After Ischemic Stroke: A Randomized, Blinded, Preclinical Study

Introduction: The angiotensin type 2 receptor (AT2R) agonist, compound 21 (C21), has been shown to be neuroprotective and neurorestorative after stroke in male rats. Here, we aim to determine the long-term impact of C21 treatment on hypertensive female rats after stroke. Methods: Twenty female ovariectomized spontaneously hypertensive rats (SHRs), 16 weeks of age, were subjected to 1h MCAO and randomized at 24h to receive either vehicle or IP C21 0.03 mg/kg for 5 days followed by oral C21 (0.12mg/kg/day) for 5 weeks in drinking water. Sensorimotor behavior tests (modified Bederson, 0-8, where 8 is normal) were performed at 24h and weekly, while cognitive assessments (Passive Avoidance and Novel Object Recognition) were performed at weeks 5 and 6. Results: (mean±SEM) All stroked animals survived and showed improved motor performance at 6 weeks, with no effect of C21. However, C21 treatment significantly improved non-spatial working memory and reference memory without an effect on anxiety level at 6 weeks post-stroke. Conclusions: AT2R stimulation using C21 improves sensorimotor function and prevents the development of cognitive impairment in ovariectomized female rats, even when initiated at 24 hours after stroke.

The role of task-irrelevant space in non-spatial working memory

The role of task-irrelevant space in non-spatial working memory

Neurons in the Hippocampus of Crows Lack Responses to Non-spatial Abstract Categories.

Lesion studies suggest a role of the avian hippocampus in spatial and episodic memory. However, whether the avian hippocampus is also involved in processing categorical information and non-spatial working memory contents remains unknown. To address this question, we trained two crows in a delayed-match-to-sample test to assess and briefly memorize the number of items in dot displays, i.e., their numerosity. We recorded neuronal activity in hippocampus while crows solved this task. Hardly any hippocampal neurons responded to the category ‘numerosity,’ during neither sample presentation, nor during the memory delay. This was in striking contrast to previous recordings in the telencephalic association area ‘nidopallium caudolaterale’ (NCL) of the same crows, in which we previously reported an abundance of numerosity-selective and working memory-selective neurons. Our data suggest that categorical information is not processed in the avian hippocampus.

Ameliorative Effect of Silymarin on Scopolamine-induced Dementia in Rats.

AIM:This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT) in rats.METHODS:The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pre-treated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioural, biochemical, histopathological, and immunohistochemical analyses were then performed.RESULTS:Rats pre-treated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin mitigated protein expression of the glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil.CONCLUSION:This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.