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Humans are reflective, adaptive, and social. They recall the past, sometimes discuss these recollections with others and become nostalgic; yet, previous research has not examined nostalgia in social media. This paper investigates the expression of nostalgia within Facebook conversations. The specific themes of nostalgic longing and the expression of personal emotions are investigated in two studies. Study 1 examines 375,857 Facebook posts, and Study 2 expands on this by comparing a sample of 10,000 Facebook and 10,000 general (non-nostalgic) posts. Content analyses of these posts reveal significant evidence of nostalgic expressions in Facebook conversations. Cluster analysis reveals newer themes of nostalgic longing related to family, life stories, historical events (presidential elections, man on the moon and Gandhi), spirituality, appreciation of life, romanticism and fun. General posts tend to focus on spontaneous, spur-of-the-moment greetings, emotions, and day of the week. Nostalgic posts, in contrast, are more reflective, more emotional, and frequently include both positive and negative emotions, which is consistent with a deeper, bittersweet character to nostalgia. The concurrent utilization of past- and present-tense words in nostalgic posts suggests that, for some Facebook users, nostalgia helps interpret and navigate present circumstances. The research concludes with theoretical and managerial implications. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Haloperidol (HAL) is an antipsychotic drug that has high affinities to the dopamine D2, but low affinities to D1 receptors in the brain. Of brain regions, caudate putamen (CP) has the highest levels of the D1 and D2 receptors. In this study we evaluated the spatial memory of C57BL/6 mice following chronic administration of HAL and measured levels of D1 and D2 receptors in specific brain regions, with the hypothesis that the D1 and D2 receptors in CP are important players in spatial memory function of the brain. Main methods: C57BL/6 mice received daily intraperitoneal injections of saline or HAL at 1.0 or 2.0mg/kg/day for 3 or 6weeks. Two days after the last injection, spontaneous alternation of mice in a Y-maze was evaluated to measure their exploratory behavior and spatial working memory. The Morris water maze test was performed to measure their spatial learning and memory. D1 and D2 receptors in specific brain regions were measured by Western-blot analysis. Key findings: HAL treatment for 6weeks decreased the spontaneous alternation of mice in Y-maze, altered the acquisition process and impaired spatial memory in Morris water maze. The same treatment increased levels of D1 and D2 receptors in CP and up-regulated D2 receptors in the hippocampus, but did not change the receptors in the prefrontal cortex. Significance: These results suggest that the D1 and D2 receptors in CP are among the main targets of HAL and the receptors in CP play an important role in spatial learning and memory. [Copyright &y& Elsevier]

In this paper, we adopt the lens of absorptive capacity (ACAP), defined by two dimensions--the knowledge base (consisting of knowledge diversity, depth, and linkages) and routines (consisting of sensing and experimentation)--to explain how a software firm's knowledge endowments influence its level of radical information technology innovation during a technological breakthrough. We distinguish three types of IT innovations--base, processes, and service innovation--that form an innovation ecology. We posit that (1) ACAP is a relational construct where the impact of the knowledge base is mediated by routines; (2) IT innovations are either externally adopted or internally generated; and (3) knowledge antecedents associated with different types of innovations differ. We hypothesize a three-step, mediated path (knowledge base → sensing → experimentation → innovation) for external innovation adoption, and a two-step path (knowledge diversity/depth → experimentation → innovation) for internal innovation creation to explain the software firm's level of radical innovation across three IT innovation types. We validate the model through a cross-sector study that examined how 121 small software firms innovated with Internet computing. We confirm the mediated nature of ACAP for external base innovations, which are driven by all three knowledge-based factors as follows: (1) knowledge depth (direct positive effect); (2) knowledge diversity (mediated three-step path), (3) knowledge linkages (mediated three step path). Process innovations are externally driven by a three-step mediated path for knowledge linkages, as well as being directly affected by knowledge diversity, but negatively and directly impeded by knowledge depth. Service innovations are not driven by any mediated influence of ACAP, but driven directly by knowledge diversity. At the same time, both service and process innovations are strongly influenced by prior IT innovations: base and/or service. Several directions for future studies of radical IT innovation are proposed. [ABSTRACT FROM AUTHOR]

A longitudinal study of middle school students examined adolescents' skepticism toward advertising and their beliefs about the persuasive tactics advertisers employ. Comparisons across grade levels and over the course of the school year indicated that knowledge about advertiser tactics developed in the direction of adult understanding. Skeptical attitudes toward advertisers' motives showed no differences across grade levels; however, students generally became more disbelieving of advertising claims as the school year progressed. The level of skepticism toward advertising was high and was positively related to having a more adult understanding of advertising tactics. [ABSTRACT FROM AUTHOR]

Rationale: There is strong evidence that nicotine can enhance cognitive functions and growing evidence that this effect may be larger in young healthy APOE ε4 carriers. However, the moderating effects of the APOE ε4 allele on cognitive impairments caused by nicotine deprivation in chronic smokers have not yet been studied with brain indices. Objective: We sought to determine whether young female carriers of the APOE ε4 allele, relative to noncarriers, would exhibit larger abstinence-induced decreases in P3b amplitude during a two-stimulus auditory oddball task. Methods: We compared parietal P3bs in female chronic smokers with either APOE ε3/ε3 (n = 54) or ε3/ε4 (n = 20) genotype under nicotine-sated conditions and after 12–17-h nicotine deprivation. Results: Nicotine deprivation significantly reduced P3b amplitudes in APOE ε4 carriers, but not in APOE-ε3/ε3 individuals, such that the difference seen prior to nicotine deprivation was eliminated. Conclusions: The results suggest that subjects with the APOE ε4 allele are more sensitive to nicotine, which could influence smoking patterns, the risk for nicotine dependence, and the cognitive effects of nicotine use in these individuals. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is the primary cause of dementia in the elderly. The cause of the disease is still unknown, but amyloid plaques and neurofibrillary tangles in the brain are thought to play a role. However, transgenic mouse models expressing these neuropathological features do not show severe or consistent cognitive impairments. There is accumulating evidence that diabetes increases the risk for developing AD. We tested the hypothesis that experimentally induced diabetes would exacerbate cognitive symptoms in a mouse model of AD. Diabetes was induced in 12-month old 3xTg mice using streptozotocin (STZ; 90 mg/kg, i.p., on two successive days). Hyperglycemia was verified by sampling blood glucose levels. Three months after injection (at 15 months of age), the mice were behaviorally tested in the Morris water maze and contextual fear conditioning. Subsequently, the hippocampal region was examined using immunohistochemistry (6E10 antibody for amyloid) and immunoblotting (AT8 antibody for phosphorylated tau). No differences were found in learning or memory between the vehicle-treated control and STZ-treated groups. A significant increase in the number of amyloid-positive plaques was observed in the subiculum of STZ-treated mice; very few plaques were seen in other hippocampal regions in either group. No differences in AT8 load were observed. These results reinforce that amyloid plaques, per se, are not sufficient to cause memory impairments. Further, while diabetes can enhance this aspect of brain pathology, the combination of disrupted glucose metabolism and the transgenes is still not sufficient to cause the severe cognitive impairments associated with clinical AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by beta-amyloid (Aβ) deposition, neurofibrillary tangles and cognitive decline. Clinical data suggests that both type 1 and type 2 diabetes are risk factors for AD-related dementia and several clinical studies have demonstrated that AD patients show alterations in peripheral glucose regulation characterized by insulin resistance (hyperinsulinemia) or hypoinsulinemia. Whether animal models of AD exhibit a pre-diabetic phenotype without additional dietary or experimental manipulation is unclear however, with contradictory data available. Further, most studies have not examined the time course of potential pre-diabetic changes relative to AD pathogenesis and cognitive decline. Thus, in this study we tested the hypothesis that a pre-diabetic phenotype (peripheral metabolic dysregulation) exists in the APP/PS1 transgenic model of AD under normal conditions and precedes AD-related pathology. Specifically, we examined glucose tolerance in male APP/PS1 mice on a C57BL/6J congenic background at 2, 4–6 and 8–9 months of age by assessing fasting glucose levels, glucose tolerance, plasma insulin levels and insulin sensitivity as well as the development of pathological characteristics of AD and verified that our APP/PS1 mice develop cognitive impairment. Here we show that APP/PS1 mice, compared to wild-type controls, exhibit a significant impairment in glucose tolerance during an intraperitoneal glucose tolerance test (ipGTT) and a trend for increased fasting plasma insulin concentrations as early as 2 months of age, while extracellular Aβ 1–42 deposition occurs later and cognitive decline exists at 8–9 months of age. Moreover, APP/PS1 mice did not respond as well to exogenous insulin as the wild-type controls during an intraperitoneal insulin tolerance test (ipITT). Taken together, these data reveal that male APP/PS1 mice on a C57BL/6J congenic background exhibit a pre-diabetic phenotype prior to the development of AD-like pathology and that this metabolic deficit persists when they exhibit neuropathology and cognitive decline. This raises the question of whether altered glucose regulation and insulin production/secretion could contribute to AD pathogenesis. [ABSTRACT FROM AUTHOR]

Exposure to early stressful adverse life events such as maternal separation severely impacts the development of the nervous system. Using immunohistochemistry, quantitative PCR and Western blot approaches, we found that alpha6 subunit-containing GABA A receptors (Gabra6-containing GABA A Rs) were expressed on hippocampal interneurons of adolescent rats. Maternal separation stress (MS) from postnatal day 2 to15 significantly reduced Gabra6 expression and provoked depressive behaviors such as anhedonia. Furosemide, the selective antagonist of Gabra6-containing GABA A Rs, strongly increased peak amplitude of evoked IPSCs at CA3-CA1 synapses and the frequency of miniature IPSPs recorded from CA1 pyramidal cells in naive control animals, and this effect was occluded in MS animals. Knockdown of Gabra6 expression in hippocampus mimicked furosemide’s effect and was sufficient to produce similar depressive symptoms that were observed in MS animals. These results indicate that the Gabra6-containing GABA A R is a key modulator of hippocampal synaptic transmission and likely plays a crucial role in the pathophysiology of maternal separation-induced depression. [ABSTRACT FROM AUTHOR]

Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems. DEAF1 is highly expressed in the CNS, especially during early embryonic development. All four mutations were missense mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the four amino acid changes showed impaired transcriptional regulation of the DEAF1 promoter. Moreover, behavioral studies in mice with a conditional knockout of Deaf1 in the brain showed memory deficits and increased anxiety-like behavior. Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1. [Copyright &y& Elsevier]

Abstract: The brain is capable of remarkable synaptic reorganization following stress and injury, often using the same molecular machinery that governs neurodevelopment. This form of plasticity is crucial for restoring and maintaining network function. However, neurodegeneration and subsequent reorganization can also play a role in disease pathogenesis, as is seen in temporal lobe epilepsy and Alzheimer''s disease. β-Secretase-1 (BACE1) is a protease known for cleaving β-amyloid precursor protein into β-amyloid (Aβ), a major constituent in amyloid plaques. Emerging evidence suggests that BACE1 is also involved with synaptic plasticity and nerve regeneration. Here we examined whether BACE1 immunoreactivity (IR) was altered in pilocarpine-induced epileptic CD1 mice in a manner consistent with the synaptic reorganization seen during epileptogenesis. BACE1-IR increased in the CA3 mossy fiber field and dentate inner molecular layer in pilocarpine-induced epileptic mice, relative to controls (saline-treated mice and mice 24–48h after pilocarpine-status), and paralleled aberrant expression of neuropeptide Y. Regionally increased BACE1-IR also occurred in neuropil in hippocampal area CA1 and in subregions of the amygdala and temporal cortex in epileptic mice, colocalizing with increased IR for growth associated protein 43 (GAP43) and polysialylated-neural cell adhesion molecule (PSA-NCAM), but reduced IR for microtubule-associated protein 2 (MAP2). These findings suggest that BACE1 is involved in aberrant limbic axonal sprouting in a model of temporal lobe epilepsy, warranting further investigation into the role of BACE1 in physiological vs. pathological neuronal plasticity. [Copyright &y& Elsevier]

Abstract: Recent findings suggest that Alzheimer''s dementia may be mediated by soluble beta amyloid (Aβ) more than the deposits of aggregated, insoluble Aβ, and vulnerability to cognitive deficits after scopolamine challenge may help identify AD even in patients that are still pre-symptomatic. The objectives of the present experiments were to determine if vulnerability to cognitive deficits after scopolamine challenge is related to levels of soluble Aβ, and if levels of soluble Aβ are more closely related to cognitive deficits than levels of insoluble Aβ, even in aged, transgenic mice, after they have developed very high levels of insoluble Aβ. Aged F-344 rats and young mice over-expressing the Swedish mutation in the human amyloid precursor protein (APPsw; Tg2576+) had elevated levels of soluble Aβ, and were more vulnerable to scopolamine challenge in the Morris water maze (MWM), relative to young rats and Tg2576− mice; but, among individual animals, higher levels of soluble Aβ were not correlated with vulnerability to scopolamine. On the other hand, in aged Tg2576+ mice, cognitive deficits were related to levels of soluble Aβ, not insoluble Aβ, despite the fact that the levels of insoluble Aβ were thousands of times higher than the levels of soluble Aβ. The results of the present experiments suggest that vulnerability to cognitive deficits after scopolamine challenge is not related to elevated levels of soluble Aβ, but that high levels of soluble Aβ are more closely correlated with cognitive deficits than the amount insoluble Aβ, even after large amounts of aggregated, insoluble Aβ have been deposited. [Copyright &y& Elsevier]

Neuroinflammation is involved in brain aging and neuronal cell death in neurodegenerative diseases such as Alzheimer's disease (AD). Butein has been suggested to have anti-inflammatory, anti-apoptotic, and anti-cancer effects. However, few studies have been done to evaluate whether butein exerts protective effects on neurons, and the potential mechanism for this effect has not been studied. Here, we examined the effect of butein on SH-SY5Y neuroblastoma cells grown with conditioned medium from BV2 microglia cells that had been activated by lipopolysaccharide (LPS) as a neuroinflammation model. We found butein pretreatment significantly increased SH-SY5Y cell viability in a dose-dependent manner by inhibiting the apoptosis normally induced by microglia-conditioned medium. SH-SY5Y cells treated with microglia-conditioned medium showed upregulated ERK signaling pathway-related mRNA expression and protein phosphorylation, which was dose-dependently reversed by butein. Immunocytochemistry and Western blot results showed that BV2-LPS conditioned medium-induced Nuclear factor kappaB (NF-κB) transactivational activity in SH-SY5Y cells, but this was attenuated by butein treatment of the BV2 cells prior to their exposure to LPS. Collectively, our results indicate that butein effectively mitigates inflammatory injury caused by LPS-conditioned medium from microglia, possibly due to reductions in the transactivational activity of NF-κB p65 and ERK signaling pathway activation, and provide evidence for a neuroprotective role of butein through blocking negative consequences of microglial activation. [ABSTRACT FROM AUTHOR]

Introduction: The neural underpinnings underlying individual differences in nicotine-enhanced reward sensitivity (NERS) and smoking progression are poorly understood. Thus, we investigated whether brain resting-state functional connectivity (rsFC.) during smoking abstinence predicts NERS and smoking progression in young light smokers. We hypothesized that high rsFC between brain areas with high densities of nicotinic receptors (insula, anterior cingulate cortex [ACC], hippocampus, thalamus) and areas involved in reward-seeking (nucleus accumbens [NAcc], prefrontal cortex [PFC]) would predict NERS and smoking progression., Aims and Methods: Young light smokers (N = 64, age 18-24, M = 1.89 cigarettes/day) participated in the study. These individuals smoked between 5 and 35 cigarettes per week and lifetime use never exceeded 35 cigarettes per week. Their rsFC was assessed using functional magnetic resonance imaging after 14 hours of nicotine deprivation. Subjects also completed a probabilistic reward task after smoking a placebo on 1 day and a regular cigarette on another day., Results: The probabilistic-reward-task assessed greater NERS was associated with greater rsFC between the right anterior PFC and right NAcc, but with reduced rsFC between the ACC and left inferior prefrontal gyrus and the insula and ACC. Decreased rsFC within the salience network (ACC and insula) predicted increased smoking progression across 18 months and greater NERS., Conclusions: These findings provide the first evidence that differences in rsFCs in young light smokers are associated with nicotine-enhanced reward sensitivity and smoking progression., Clinical Trial Registration: NCT02129387 (preregistered hypothesis: www.clinicaltrials.gov)., Implications: Weaker rsFC within the salience network predicted greater NERS and smoking progression. These findings suggest that salience network rsFC and drug-enhanced reward sensitivity may be useful tools and potential endophenotypes for reward sensitivity and drug-dependence research., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Students with neurodevelopmental disorders [Specific Learning Disorders (SLD), Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD)] often experience learning challenges due to underlying weaknesses in cognitive processes. As these are some of the most common conditions to impact functioning, the development of effective treatments is a priority for neuropsychologists. However, the task of designing effective cognitive interventions has proven one of the most difficult challenges for our field. The Arrowsmith Program uses a novel approach compared to other cognitive intervention programs. We hypothesized that intensive practice of one aspect of this program would lead to improved cognitive functions in students with neurodevelopmental disorders. Twenty-seven students with neurodevelopmental disorders (ages 9.4-18.4 years) were recruited from Arrowsmith schools. Cognitive baseline and post-intervention data were gathered using components of the Woodcock-Johnson IV Tests of Cognitive Abilities. The intervention consisted of 6 weeks of intensive practice of the Symbol Relations Task. W-scores were used in a paired sample t -test analysis to determine if cognitive skill improvement occurred. Significant improvements were found in several measures of neuropsychological assessment, in particular in the Cattell-Horn-Carroll broad abilities These results provide a foundation for further work examining the utility of this novel approach to cognitive intervention.

β-amyloid precursor protein (APP) and presenilins mutations cause early-onset familial Alzheimer's disease (FAD). Some FAD-based mouse models produce amyloid plaques, others do not. β-Amyloid (Aβ) deposition can manifest as compact and diffuse plaques; it is unclear why the same Aβ molecules aggregate in different patterns. Is there a basic cellular process governing Aβ plaque pathogenesis? We showed in some FAD mouse models that compact plaque formation is associated with a progressive axonal pathology inherent with increased expression of β-secretase (BACE1), the enzyme initiating the amyloidogenic processing of APP. A monoclonal Aβ antibody, 3D6, visualized distinct axon terminal labeling before plaque onset. The present study was set to understand BACE1 and axonal changes relative to diffuse plaque development and to further characterize the novel axonal Aβ antibody immunoreactivity (IR), using triple transgenic AD (3xTg-AD) mice as experimental model. Diffuse-like plaques existed in the forebrain in aged transgenics and were regionally associated with increased BACE1 labeled swollen/sprouting axon terminals. Increased BACE1/3D6 IR at axon terminals occurred in young animals before plaque onset. These axonal elements were also co-labeled by other antibodies targeting the N-terminal and mid-region of Aβ domain and the C-terminal of APP, but not co-labeled by antibodies against the Aβ C-terminal and APP N-terminal. The results suggest that amyloidogenic axonal pathology precedes diffuse plaque formation in the 3xTg-AD mice, and that the early-onset axonal Aβ antibody IR in transgenic models of AD might relate to a cross-reactivity of putative APP β-carboxyl terminal fragments.

Eyeblink conditioning is a relatively simple form of associative learning that shows neurobiological and behavioral parallels across several species, including humans. Aged subjects acquire eyeblink conditioning more slowly than young ones. In addition, eyeblink conditioning effectively discriminates patients with Alzheimer's disease from healthy older adults. The present study evaluated the effect of a novel L-type Ca2+ channel antagonist, MEM 1003, on delay and trace eyeblink conditioning in older (mean 33.4 months old) female New Zealand white rabbits. In the delay conditioning paradigm, an 850 ms tone conditioning stimulus (CS) was followed 750 ms after its onset by a 100 ms corneal air puff. Several trace conditioning paradigms were evaluated, with a silent period of 300, 400 or 500 ms between the end of the tone CS and the delivery of the air puff. Learning was more difficult in the longer trace paradigms than in the delay paradigm. MEM 1003, at a dose of 2.0 mg/kg, s.c., given daily 30 min prior to training on each of the 15 training days, enhanced learning compared to vehicle injections in both delay and trace paradigms. However, higher or lower doses were ineffective. These results support previous work demonstrating that modulation of Ca2+ channel activity can reduce age-related cognitive impairments.

Rationale: Alzheimer's dementia (AD) patients have profound deficits in cognitive and social functions, mediated in part by a decline in cholinergic function. Acetylcholinesterase inhibitors (AChEI) are the most commonly prescribed treatment for the cognitive deficits in AD patients, but their therapeutic effects are small, and it is still not clear if they primarily affect attention, memory, or some other cognitive/behavioral functions., Objectives: The objective of the present experiments was to explore the effects of donepezil (Aricepttrade mark), an AChEI, on behavioral deficits related exclusively to cholinergic dysfunction., Materials and Methods: The effects of donepezil were assessed in Sprague-Dawley rats with scopolamine-induced deficits in a battery of cognitive/behavioral tests., Results: Scopolamine produced deficits in contextual and cued fear conditioning, the 5-choice serial reaction time test, delayed nonmatching to position, the radial arm maze, and the Morris water maze. Analyses of the pattern and size of the effects revealed that donepezil produced very large effects on scopolamine-induced deficits in psychomotor function (approximately 20-50% of the variance), moderate-sized effects on scopolamine-induced deficits in simple conditioning and attention (approximately 3-10% of the variance), but only small effects on scopolamine-induced deficits in higher cognitive functions of working memory and spatial mapping (approximately 1% of the variance)., Conclusions: These results are consistent with the limited efficacy of donepezil on higher cognitive function in AD patients, and suggest that preclinical behavioral models could be used not only to determine if novel treatments have some therapeutic potential, but also to predict more precisely what the pattern and size of the effects might be.

An effective treatment for age-related cognitive deficits remains an unmet medical need. Currently available drugs for the symptomatic treatment of Alzheimer's disease or other dementias have limited efficacy. This may be due to their action at only one of the many neurotransmitter systems involved in the complex mechanisms that underlie cognition. An alternative approach would be to target second messenger systems that are utilized by multiple neurotransmitters. Cyclic adenosine monophosphate (cAMP) is a second messenger that plays a key role in biochemical processes that regulate the cognitive process of memory consolidation. Prolongation of cAMP signals can be accomplished by inhibiting phosphodiesterases (PDEs). Eleven PDE families, comprised of more than 50 distinct members, are currently known. This review summarizes the evidence demonstrating that rolipram, a selective inhibitor of cAMP-selective PDE4 enzymes, has positive effects on learning and memory in animal models. These data provide support for the general approach of second messenger modulation as a potential therapy for cognitive dysfunction, and specifically suggest that PDE4 inhibitors may have utility for improving the symptoms of cognitive decline associated with neurodegenerative and psychiatric diseases.

Hippocampal-dependent learning and memory deficits have been well documented in aging rodents. The results of several recent studies have suggested that these deficits arise from weakened synaptic plasticity within the hippocampus. In the present study, we examined the relationship between hippocampal long-term potentiation (LTP) in vitro and spatial learning in aged (24-26 months) Fischer 344 rats. We found that LTP induced in the CA1 region using theta-frequency stimulation (5 Hz) is selectively impaired in slices from a subpopulation of aged rats that had shown poor spatial learning in the Morris water maze. LTP at 5 Hz in aged rats that did not show learning deficits was similar to that seen in young (4-6 months) controls. We also found that 5 Hz LTP amplitude strongly correlated with individual learning performance among aged rats. The difference in 5 Hz LTP magnitude among aged rats was not attributable to an altered response to 5 Hz stimulation or to differences in the NMDA receptor-mediated field EPSP. In addition, no performance-related differences in LTP were seen when LTP was induced with 30 or 70 Hz stimulation protocols. Finally, both 5 Hz LTP and spatial learning in learning-impaired rats were enhanced with the selective muscarinic M2 antagonist BIBN-99 (5,11-dihydro-8-chloro-11-[[4-[3-[(2,2-dimethyl-1-oxopentyl)ethylamino]propyl]-1-piperidinyl]acetyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one). These findings reinforce the idea that distinct types of hippocampal LTP offer mechanistic insight into age-associated cognitive decline.