Translational inhibition has been suggested to impair long-term memory (LTM) while leaving short-term memory (STM) unaffected. However, intracranial infusions of protein synthesis inhibitors such as anisomycin (ANI), cycloheximide, and emetine have been shown to profoundly suppress both spontaneous and evoked neural activity, likely due to impairments of mitochondrial function and cellular metabolic loss. Given this neural suppressive effect, we wanted to re-examine the influence of translational inhibition on acquiring and retaining novel information with a direct comparison to agents that simply inactivate neural activity (without affecting protein synthesis). Our model was the widely-used cue fear conditioning paradigm which is known to be dependent on the basolateral amygdala complex (BLA). Using male rats, we compared the behavioral deficits in cued fear conditioning induced by intra-BLA infusions of ANI to other commonly used neural inactivators, including the GABAA agonist muscimol (MUSC) and the sodium channel blocker tetrodotoxin (TTX). We confirmed that intra-BLA infusions of ANI and MUSC suppressed neural activity by examining effects on spiking activity in the BLA. In behavioral experiments, pre-training bilateral BLA infusions of ANI impaired both short-term (2 h) and long-term (24 h) cued fear memory similarly to the effects observed with both MUSC and TTX. Our results suggest that reductions in neural activity, whether via GABAA agonism, sodium channel blockade, or translational inhibition, are essential for both short- and long-term memory. Consequently, the influence of translational inhibitors may be better understood as being mediated via neural inactivation rather than solely the result of the absence of de novo synthesis of plasticity-related proteins. Previous work that interprets results using translational inhibitors as being purely protein-synthesis-dependent must to be reconsidered. SIGNIFICANCE STATEMENT: The axiomatic idea that protein synthesis can distinguish between phases of memory, namely short- versus long-term forms, is entirely based on work purporting to show differential disruptive effects of translational inhibitors on retrieval tested at long, but not short-term delays. However, protein synthesis inhibitors profoundly suppress neural activity as well, which should have an equivalent detrimental effect on both short- and long-term memory. In this study, we demonstrate that the translational inhibitor anisomycin suppresses neural activity in the basolateral amygdala which results in deficits in both short- and long-term memory for conditioned fear, similarly to agents that ONLY block neural activity. These findings are consistent with an important and under-appreciated role of neural activity in memory processes and argue for a critical re-evaluation of the strict de novo protein hypothesis of memory consolidation.
Cognitive maps support inference and planning by representing associations between experiences encoded in memory. These map-like representations are thought to carry information not only about directly observed links but also about longer paths. The ability to make judgments based on multi-step associations varies with one's experience in an environment and with changes in memory abilities across the lifespan. However, it remains unclear exactly how representations of associative structure are influenced by learning curricula and memory constraints. Prior studies have suggested a tradeoff: memory representations can either be more integrated to improve inference, or more separated to recall distinct direct associations. Whether overlapping associations are experienced nearby in time (interleaved) or spaced apart (blocked) can bias memory representations toward integration or separation. However, key recent findings about how blocked versus interleaved experience bias integration or separation have been inconsistent. Here, we introduce a computational framework that helps reconcile these apparent discrepancies. Using neural network simulations of three separate memory-guided inference tasks, we show that variations in memory capacity and the sparsity of neural codes interact with learning sequence to shape network representations. Specifically, blocked learning promotes integration when memory capacity is low, while interleaved learning promotes integration when memory capacity is high. Integration is especially likely to result from representations formed when neural codes are both sparse and distributed. These results offer a principled computational account of how flexible, map-like representations can arise from experience and suggest avenues for individualized memory interventions to improve inference, generalization, and planning.
Episodic memory is the conscious recalling of past experiences. The neural underpinnings of this skill have long been of clinical interest, as deficits can be debilitating, including to those with temporal lobe pathology. This study sought to improve the assessment of those with unilateral temporal lobe pathology by comparing the localisation and lateralisation of successful spatial and verbal associative recognition memory using 3D time-frequency analysis and connectivity analysis of EEG data, while reducing perceptual confounds. Twenty right-handed participants aged 18 to 33 years were included. Average band-power analysis in eLORETA was used to compare verbal associative memory, spatial associative memory, and the resting state to identify the regions of interest for subsequent analyses. Time-frequency analyses were conducted for the inferior temporal, parahippocampal, inferior frontal, and middle occipital gyri. Phase-synchronisation was compared between conditions between 32 regions of interest. Material specific differences in neural synchrony were identified, with peak synchronisation around 1000 ms that was unique to verbal associative memory and mildly left-lateralised, compared with temporally diffuse and bilateral desynchronisation during spatial associative memory. However, overall, levels of local synchrony during verbal and spatial associative memory were more similar than different, with no compelling evidence for dissociation by material type or hemisphere. Differences in phase-synchronisation between verbal and spatial associative memory for theta and alpha oscillations suggested their role in long-range rather than local synchrony. Future research should focus on replication, further explore connectivity, and assess material-specific deficits in perceptual processing to identify deficits in memory processing.
Positive and negative schizotypy reflect distinct patterns of subclinical traits in the general population associated with neurodevelopmental and schizophrenia-spectrum pathologies. Yet, a comprehensive characterization of the unique and shared neuroanatomical signatures of these schizotypy dimensions is lacking. Leveraging 3D brain MRI data from 2730 unmedicated healthy individuals, we identified neuroanatomical profiles of positive and negative schizotypy and systematically compared them with disorder-specific, microarchitectural, neurotransmitter-level, and connectome measures. Positive and negative schizotypy were associated with distinct cortical signatures, of predominantly thinner frontal and thicker paralimbic cortical areas, respectively. These cortical signatures of positive and negative schizotypy were differentially linked to brain-wide cortical patterns of schizophrenia-spectrum (clinical high-risk for psychosis, schizophrenia) and neurodevelopmental conditions (ADHD, autism spectrum disorder and 22q11.2 deletion syndrome). Additionally, the positive and negative schizotypy-related cortical profiles mapped onto different local attributes of gene expression, cortical myelination, D1, and histamine receptor distributions. Network models further showed that positive and negative schizotypy cortical signatures were spatially associated with cortical hubs, suggesting that highly interconnected regions are more vulnerable to the morphological differences associated with both schizotypy dimensions. Finally, predominantly sensorimotor-to-association and paralimbic areas emerged as epicenters with connectivity profiles significantly linked to the schizotypy-related cortical patterns. Collectively, this study identified cortical signatures of positive and negative schizotypy traits that are embedded along multiple scales of cortical organization and neuropsychiatric pathologies. Our work yields novel insights into how neurobiology and brain architecture may guide neuroanatomical vulnerability and resilience to psychopathology in the general population.
Mild traumatic brain injury (mTBI) causes deficits in memory formation and retrieval by disrupting the balance in synaptic excitability and inhibition. The pre-trauma endogenous opioid tone could influence the severity of post-trauma cognitive deficits. Thus, the current investigation aimed to evaluate how post-mTBI adaptations in opioid receptor subtype signaling affect the severity of memory dysfunction depending on the endogenous opioid tone. For this purpose, we utilized adult male mice divergently bred for high (HA) and low (LA) endogenous opioid system activity. Mild traumatic brain injury was induced by a mechanical impact to the temple. Memory formation and retrieval were assessed in the Morris Water Maze and Novel Object Recognition tasks. Contribution of opioid µ-, δ- and κ- receptor subtypes was studied by administration of selective opioid receptor antagonists - cyprodime, naltrindole or nor-binaltorphimine prior to mTBI. Expression and activation of opioid receptor subtypes were quantified by qPCR and the [35S]GTPγS assay. LA mice experienced more severe post-mTBI spatial learning deficits accompanied by diminished signaling from all three receptor subtypes in the hippocampus. Alterations in µ- or δ-opioid receptor signaling in the medial prefrontal cortex did not differentiate the lines in terms of recognition memory or spatial memory retrieval. In HA mice, both spatial memory formation and retrieval were improved with selective µ- opioid receptor blockage, while restoration of recognition memory was related to either µ- or δ-opioid receptor inhibition. In conclusion, bidirectional selection for the endogenous opioid tone creates line-dependent alterations in opioid receptor subtype-mediated regulation of memory processes.
In this work, we develop a mathematical model that captures both the early and late phases of Long-Term Potentiation (LTP) and Long-Term Depression (LTD), incorporating NMDAR-dependent induction and changes in AMPAR conductance. The model combines multiple essential properties. First, it emphasizes a detailed representation of biochemical processes within the postsynaptic neuron, thereby illustrating the interaction between LTD and distinct forms of LTP. Second, the dynamic modulation of postsynaptic AMPA receptor conductance is represented through nonlinear differential equations and algebraic relations. Third, the model incorporates input specificity, associativity, and cooperativity, allowing synaptic changes at one site to influence the strength of neighboring synapses. These features provide a comprehensive description of synaptic dynamics, allowing the simulation of plasticity at both the cellular and the network levels. Overall, the model offers a valuable framework for studying NMDAR-dependent LTP and LTD by explicitly incorporating changes in AMPAR conductance. We believe that this model provides deeper insights into the molecular mechanisms of synaptic plasticity and paves the way for the construction of network-level models by linking multiple cells through AMPA receptor conductance. Significance statement: We present a comprehensive mathematical framework that integrates early (E-LTP), late (L-LTP), and LTD by incorporating NMDAR-dependent signaling and changes in AMPAR conductance. By combining and extending established biochemical models, our approach links molecular signaling, receptor trafficking, and postsynaptic membrane dynamics to changes in synaptic strength. The model reproduces key experimental phenomena, including input specificity, associativity, and cooperativity, and clarifies how pathways, such as CaMKII and PKA govern the stability of synaptic modifications. By capturing both cellular- and network-level properties, this framework provides a foundation for building scalable neural models grounded in the biophysics of learning and memory.
Behavioral flexibility is critical for adaptive functioning and is often impaired in neuropsychiatric disorders such as obsessive-compulsive disorder (OCD). The serotonergic agent meta-chlorophenylpiperazine (mCPP), a non-selective 5-HT receptor agonist, is commonly used to model OCD-like behaviors. However, its effects on behavioral flexibility, particularly in females, remain poorly understood. This study investigated sex differences and the effects of mCPP on acquisition and reversal learning in adult Wistar rats using the T-maze task. Experiment 1 compared male and female rats during the acquisition and reversal learning phases. Experiment 2 evaluated the effects of mCPP (0.5 and 2 mg/kg) on behavioral flexibility in males and females. Behavioral measures included accuracy, omissions, and reaction time. In Experiment 1, no significant differences were observed between males and females during acquisition or reversal learning. In Experiment 2, mCPP at 2 mg/kg impaired reversal learning in males, as shown by increased omissions and reaction time. In females, the same dose disrupted both acquisition and reversal learning, with increased omissions and reaction time, and reduced accuracy. These findings indicate that mCPP disrupted cognitive performance in both sexes, with more pronounced and broader impairments in females. These results highlight the importance of including both sexes in preclinical models for behavioral flexibility and support the relevance of serotonergic modulation in vulnerability to behavioral inflexibility.
Brief periods of offline wakeful rest following learning reliably enhance declarative memory consolidation and retention compared to online cognitively demanding post-encoding tasks. The influence of individual differences, including affective states, on this process remains under-researched, but emerging evidence suggests that trait anxiety may play a moderating role in rest effects on memory. The contribution of state anxiety - during both offline and online states - to awake consolidation remains to be established. The present study investigated whether state anxiety during post-learning wakeful rest and task engagement influences declarative memory consolidation. In a counterbalanced repeated-measures design, adults with no clinical presentation of anxiety encoded wordlists followed by either a wakeful rest period or an active task. State anxiety was measured during each post-encoding condition using a standardised self-report scale, and delayed recognition was used to assess memory retention via a signal detection approach. As expected, hit rates were modestly higher following wakeful rest than task engagement although overall recognition sensitivity (d') did not differ significantly. Crucially, hit rates and d' scores following wakeful rest varied non-linearly with state anxiety: moderate anxiety impaired memory, whereas low and high anxiety preserved it. No such non-linear relationship was observed for false alarm rates or for any memory outcomes in the task engagement condition, and contrary to previous research, trait anxiety did not influence memory. These findings suggest that while wakeful rest supports awake consolidation, the internal affective state - specifically moderate levels of anxiety - may disrupt the mental processes conducive to early memory stabilisation.
The precise coordination of slow oscillations (SO) and sleep spindles during non-rapid eye movement (NREM) sleep supports memory consolidation and may serve as a sensitive marker of cognitive aging. However, longitudinal changes in their oscillatory dynamics in midlife and older age remain poorly understood. Using polysomnography with high-density EEG at two timepoints over ~2.5 years, we examined changes in local NREM slow wave (SW), sleep spindle (occurring in the 11-16 Hz sigma range), and SO-sigma coupling strength in cognitively unimpaired middle-aged to older adults at risk for Alzheimer's disease. Fronto-central SO-sigma power coupling strength significantly declined over time, independent of changes in multiple measures of SW and sleep spindle expression. Local declines in multiple sleep spindle measures were also observed. Greater baseline levels of cerebrospinal fluid (CSF) neurogranin, a postsynaptic protein abundantly expressed in the dendritic spines of the hippocampus and cerebral cortex and implicated in calcium-dependent synaptic plasticity, predicted the magnitude of longitudinal decline in SO-fast sigma coupling strength, which in turn predicted episodic memory performance changes. These findings suggest that longitudinal changes in local sleep oscillatory dynamics are related to decreased synaptic integrity and may serve as an early indicator of memory decline in older adults at risk for Alzheimer's disease.
Reactivation of recently acquired memories during sleep supports their longevity. Reactivation can be altered during sleep using odours or sounds through a technique termed targeted memory reactivation (TMR). Here, we attempted to selectively weaken memories by reactivating them together with forgetting instructions. We delivered sounds to reactivate spatial memories and concurrent odours to reactivate instructions. Participants learned about the instructions in a Directed-Forgetting task performed with a list of to-be-remembered and to-be-forgotten words. One odour was linked with instructions to forget, one with instructions to remember, and a third was not assigned any meaning. During a nap, sounds previously linked with object-location learning were simultaneously presented with these odours. Spatial recall was tested after sleep. Sound cues produced a selective recall benefit for weakly encoded memories. However, memory results did not support the prediction that forgetting could be instilled by the concurrent Forget odour. An encoding-strength-dependent benefit was largest when sounds were presented together with the odour that lacked assigned meaning, whereas the other two odours both disrupted sound-induced memory reactivation. These two odours were linked with instructions and with multiple learning episodes in the Directed-Forgetting task. Accordingly, we infer that reactivation evoked by the Remember and Forget odour cues interfered with the reactivation of spatial memories. Odours also induced a prolonged decline in sigma EEG power (12-16 Hz) that continued at least 10 s after odour offset. Overall, these findings highlight the complexity of memory consolidation during sleep when multiple memories and multiple cues are involved.
Cognitive flexibility is a core executive function vital for adaptation and adjustment to new information. The brain-derived neurotrophic factor (BDNF) single nucleotide polymorphism, val66met, has been suggested to modulate cognitive flexibility but it remains unclear how confounding variables such as stress and sex influence this relationship. Environmental enrichment (EE) may protect against stress-induced effects. The aim of this study was to test whether BDNF val66met alters reversal learning, a key component of cognitive flexibility, when tested under stressful water maze conditions. We used a Sprague Dawley val66met rat model where pregnant val/met dams were moved to either low or high EE environments. Dams and offspring stayed in these environments until weaning, after which the offspring was moved to standard, moderate enrichment housing. Adult male and female val/val, val/met and met/met offspring then underwent a water maze reversal learning protocol. All groups rapidly learned the new location of the platform. Mediation analysis showed the relationship between val66met and cognitive flexibility was mediated by differential use of spatial strategies. Sequential clustering analysis demonstrated that val66met interacted with sex to predict cognitive flexibility performance with lower flexibility in met/met males and val/met females compared to other genotypes. EE was not a strong promotor of cognitive flexibility. Water maze testing increased corticosterone levels, confirming the stressful nature of the test. This study demonstrates the importance of considering stress and sex when investigating the role of BDNF val66met in cognitive flexibility.
Acute physical exercise (PE) is known to influence the expression of many neurobiological markers and cognitive functions, but the time course and domain-specificity of such effects remain under debate. This study investigated whether a single bout of maximal incremental exercise can increase serum brain-derived neurotrophic factor (BDNF) levels, improving cognitive performance in healthy adults. Twenty-eight physically active males underwent a maximal incremental cycling test. BDNF serum concentrations were measured at three timepoints: before exercise, 15 min after, and 24 h post-exercise. Cognitive performance in verbal and visuo-spatial memory and convergent creative thinking was assessed before and 24 h post-exercise. Results showed a significant increase in serum BDNF 24 h after exercise, while no significant change was observed 15 min post-exercise. Cognitive assessments revealed improvements in verbal immediate recall and visuo-spatial working memory, but not in long-term verbal memory, visuo-spatial short-term memory, and convergent creative thinking. No significant correlations emerged between BDNF changes and cognitive performance changes. The dissociation between BDNF and behavior points to complex and likely time-dependent mechanisms underlying exercise-induced cognitive enhancements. These results support the effectiveness of acute PE as stimulus for BDNF neurotrophin production and as a non-pharmacological tool to boost specific cognitive functions, with implications for optimizing learning and cognitive performance in healthy populations.
In the era of artificial intelligence, synthetic visual content is increasingly produced by generative technologies. An important question is how older adults process and remember such restructured novel objects, and which cognitive and neural factors are associated with successful memory. In two studies, young and older adults completed a restructured object memory task in which objects varied in schema deviation: not restructured (NR), reasonably restructured (RR), and unreasonably restructured (UR). Study 1 showed that schema deviation did not affect young adults' true object memory, whereas older adults exhibited a graded decline (NR > RR > UR). Study 2 replicated the age-sensitive pattern under time-limited responding. However, the RR advantage of older adults over UR was no longer evident. This pattern is consistent with the possibility that response deadlines shift the decision processes used to discriminate targets from within-triad lures. Study 2 also used structural MRI to test whether individual differences in the thickness of the lateral prefrontal cortex (LPFC)-specifically the left ventrolateral (LVLPFC) and right dorsolateral (RDLPFC) regions-are related to memory outcomes. Across participants, greater LVLPFC and RDLPFC cortical thickness was associated with higher true object memory and fewer schema-consistent false memories. Together, these findings suggest that increasing schema deviation disproportionately challenges episodic memory in older adults and that individual differences in LPFC cortical thickness are related to individual differences in memory accuracy. These results generate testable hypotheses about how schema-consistent versus schema-deviating designs may affect memory and decision-making tendencies differently in older adults under time constraints.
Recent studies suggest pigeons undergo age-related changes in hippocampal function and cognitive decline. The present research compared the behavior of six young and six old homing pigeons that were trained to locate food in an open-field task. The availability of the food varied by location between two different conditions: in one condition, the risky location (75% chance of food) yielded more total reward compared to a food bowl that delivered a small amount of food on all trials; in the other, the risky location (25% chance of food) yielded less total reward compared to a food bowl that delivered a small amount of food on all trials. There was no significant difference between the two experimental groups with respect to error rates (choosing an empty food location). However, while older pigeons preferred the small, constant reward location in both the low and high variable conditions, young pigeons only preferred the small, constant reward location in the low variable condition. In the high (75%) variable condition, younger, but not older, pigeons preferred the large, variable reward location, which yielded a larger long-term food gain. The behavior of the older pigeons indicates a deviation from rational decision-making and a greater aversion to risk. Further research will be necessary to probe how the avian hippocampus and related structures evaluate risk and reward, and how that evaluation may change as a function of age.
Use of fungal mycelium as a vaccination adjunct may constitute a novel antiviral strategy to address newly emerging viruses. We evaluated safety and feasibility of a fungal mycelium-based natural product (Fomitopsis officinalis and Trametes versicolor, FoTv) as an adjunct to human COVID-19 vaccination, as well as its impact on vaccine side-effects and anti-SARS-CoV-2 antibodies (Abs). Randomized, double-blind, placebo-controlled clinical trial involving adjunctive treatment with FoTv or visually-identical Placebo (dosage: eight 500-mg capsules TID orally for four days) in combination with COVID-19 vaccination. Main outcomes included: Safety (adverse events, renal and hepatic function [Days 1–14]); Feasibility (completion rate and treatment adherence); Side-effects (number and severity, self-reported on days 1 [vaccination] to 5); and anti-SARS-CoV-2 Ab levels (receptor-binding domain and Spike, collected from blood drawn on days 1, 3, 14, and 28/42, and at 6 months). Ninety participants receiving COVID-19 vaccination were randomized to either FoTv (N = 52) or Placebo (N = 38) groups. There were no adverse events and the groups had overlapping 95% confidence intervals for the percentage of participants transitioning from normal to abnormal renal/hepatic function when comparing Days 1 and 14. All participants (100%) completed the study and treatment adherence was greater than 95%. Participants with detectable anti-SARS-CoV-2 Abs (from prior COVID antigen exposure) were classified as “COVID-Exposed” and those with undetectable anti-SARS-CoV-2 Abs as “COVID-Naive.” FoTv, versus Placebo, significantly reduced side-effects in COVID-Naive individuals, specifically on days 3 and 5, but not in COVID-Exposed individuals. In the COVID-Naive FoTv group, Ab responses were preserved across 6 months (and possibly increased), an effect not observed among other groups. After COVID-19 vaccination, adjunctive FoTv was safe, feasible, and reduced vaccine side-effects without compromising (and possibly increasing) Ab levels up to 6 months in participants without previous SARS-CoV-2 exposure. Use of fungal mycelia was successfully tested as a unique approach to prevent a novel pandemic virus (SARS-CoV-2), with potential application to H5N1/Bird Flu and other emerging viruses. Trial registered on ClinicalTrials.gov NCT04951336 on June 30, 2021. The online version contains supplementary material available at 10.1186/s12865-026-00809-9.
Chromatin-modifying and -remodeling machineries are important for learning-induced transcriptional activity, yet it remains unclear how they coordinate to drive de novo gene expression for memory formation. Here, we examine the transcription factor known as calcium-responsive transactivator (CREST) in memory formation, synaptic plasticity, and learning-induced gene expression. CREST is known to bind major chromatin-modifying and -remodeling machineries via interaction with CREB-binding protein (CBP) and brahma-related gene 1 (BRG1), respectively. In silico modeling of CREST identified tyrosine 397 (Y397) within the CBP-binding domain. Expression of a CREST Y397F point mutant impairs long-term potentiation and memory. Conversely, expression of a CREST Y397D point mutant enhances memory in a CBP-dependent manner. Differential gene expression analysis reveals distinct CREST Y397-regulated signatures during memory consolidation. CBP acts through CREB and post-translation modifications to affect memory, but the findings of this study argue for consideration of the CREST-CBP interaction and Y397 accessibility as factors in memory processes.
Memory reconsolidation is a re-stabilization phase in which memory is gradually changed from unstable to stable. This process is critical because unstable memories can be subject to modification or erasure if the reconsolidation phase is disrupted within a 6 h time window. TrkB signaling pathway plays a key role in regulating neurogenesis, neuronal differentiation, maturation and survival. Numerous studies have reported that the TrkB signaling pathway participates in memory acquisition, consolidation and storage, although its role in memory reconsolidation is not fully understood. ANA-12, as a type of TrkB receptor inhibitor, can regulate various pain behaviors and attenuate propofol-induced apoptosis by blocking the TrkB signaling pathway. In this study, we investigated the effect of ANA-12 on memory reconsolidation in a novel object recognition (NOR) task. The results showed that ANA-12 injection immediately after the reactivation phase of the NOR task inhibited memory reconsolidation, whereas ANA-12 injection 6 h after the reactivation phase had no effect on memory performance. ANA-12 injection 24 h after the sample phase, with no subsequent reactivation phase, had no effect on memory performance. Transcriptome analysis demonstrated that ANA-12 administration significantly upregulated 347 genes and downregulated 79 genes in the hippocampus, compared to vehicle-treated animals. Those differentially expressed genes are involved in a wide range of functional pathways, including neuroinflammation, neurotransmitter synthesis, metabolism and transport, and long-term potentiation, which are all linked to memory impairment. These findings indicate that ANA-12-induced impaired memory reconsolidation is associated with changes in multiple signaling pathways.
Although learning over multiple days is more effective than a single day of training, the underlying cellular mechanisms of repeated training trials remain poorly understood. With a combination of empirical and computational approaches, we determined a critical time window for a second stimulus block of a multiday training protocol to augment long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse and long-term enhancement of neuronal excitability (LTEE), two cellular correlates of learning and memory. A second stimulus block delivered 24 h after the first block significantly enhanced LTF and LTEE, but was without effect at 18 or 32 h. This spacing effect appears due, at least in part, to the dynamics of competition between the transcription activator cAMP response element-binding protein 1 (CREB1) and repressor CREB2. The timer mechanism is intrinsic to individual neurons, as LTEE exhibited this critical temporal window in isolated sensory neurons. These findings suggest the dynamics of transcription factors function as a cellular timer that establishes a window of eligibility for a second learning trial to enhance memory.
Pavlov's research on how arbitrary stimuli elicit conditioned reflexes has revolutionized the field of learning. His original work with the orienting response set the foundation for further investigations on the nature of Pavlovian conditioned responding.Where Pavlov's research may have lacked the ecological significance of Pavlovian conditioning, the behavior systems approach emerged later to capture how conditioning is embedded into a broader spectrum of naturalistic behaviors.The behavior systems approach proposes that behaviors evolved as organized systems designed to solve specific adaptive problems, and that learning interacts with these systems. The approach emphasizes the arrangement of responses to stimuli in the environment on a temporal and spatial continuum from an appetitive general search behavior at one end to focal and consummatory acts at the other end.During Pavlovian conditioning, a conditioned stimulus may become integrated along the continuum.The current paper describes several studies of Pavlovian conditioning that support the behavior systems approach with more detail in studies on sexual conditioning in male quail. Collectively, these studies demonstrate the importance of the form and relevance of the CS and the CS-US interval in determining where along the continuum the CS becomes integrated and thereby determine the nature or topography of the conditioned response.These studies, and many others, should serve as a reminder of how Pavlov's research set the framework for the conceptualization of behavior systems.
LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, intersex, asexual, and related identities) individuals in science face unique career challenges. We surveyed a large sample (N = 428) of neuroscientists, uniquely capturing a diverse international population (hundreds of participants from Europe and the USA; more than 60 transgender participants). In the USA, compared to Europe, we found higher institutional support and a higher likelihood of being out of the closet in academic settings. However, participants based in the USA also reported more negative workplace experiences. A concerning 15% of the participants reported experiencing harassment at their workplace. Thematic analysis of qualitative responses showed that reasons for not being out varied by group; for example, asexual people were more likely to mention a lack of understanding, while transgender people reported safety concerns. The majority of participants (67.3%) felt that legislation affected decisions within their scientific career, with most of these participants reporting moving away from locations unsupportive of LGBTQIA+ individuals or forgoing career opportunities in certain locations. Overall, we show differential experiences of neuroscientists between the USA and Europe, as well as between identities. While our results demonstrate the challenges many LGBTQIA+ individuals in neuroscience face, they also put forward actionable recommendations for institutions that could vastly improve the lives and careers of LGBTQIA+ neuroscientists.