Short-term Habituation Research Articles

Acute optogenetic induction of the prodromal endophenotype of CA1 hyperactivity causes schizophrenia-related deficits in cognition and salience attribution.

Hyperactivity of the human anterior hippocampus has been reported to spread from its CA1 subfield to the subiculum around the onset of first-episode psychosis and could be a cellular target for early therapeutic intervention in the schizophrenia prodrome. However, to what extent CA1 hyperactivity actually causes schizophrenia-related symptoms remains unknown. Here, we mimic this endophenotype by direct optogenetic activation of excitatory cells in the homologous mouse region, ventral CA1 (vCA1) and assess its consequence in multiple schizophrenia-related behavioural tests. We find that hyperactivity of vCA1 causes hyperlocomotion and impairments of spatial and object-related short-term habituation (spatial novelty-preference and novel-object recognition memory) and spatial working memory, whereas social interaction, spatial exploration, and anxiety remain unaltered. Stimulation of the ventral subiculum, in contrast, only increased locomotion and exploration. In conclusion, CA1 hyperactivity may be a direct driver of prodromal cognitive symptoms and of aberrant salience assignment leading to psychosis.

How a pilot’s brain copes with stress and mental load? Insights from the executive control network

In aviation, mental workload and stress are two major factors that can considerably impact a pilot’s flight performance and decisions. Their consequences can be even more dramatic in single-pilot aircraft or with the forthcoming single-pilot operations where the pilot will fly alone and will not be able to be assisted in case of difficulty. An accurate and automatic monitoring of the pilot’s mental state could help to prevent the potentially dangerous effects of an excess mental workload and stress. For example, some tasks could be allocated to automation or to a ground-based flight crew if a mental overload or significant stress is detected. In the current study, the brain activity of 20 private pilots was recorded with a fNIRS device during two realistic flight simulator scenarios. The mental workload was manipulated with the added difficulty of a secondary task and stress was induced by a social stressor. Our results confirmed the sensitivity of the fNIRS readings to variations in the mental workload, with increased HbO2 concentration in regions of the executive control network (ECN), in particular in the dorsolateral prefrontal cortex and in lateral parietal regions, when the difficulty of the secondary task was high. The social stressor also triggered an HbO2 increase in the ECN, especially when it was combined with high mental workload. This latter result suggests that mental workload and stress together can have cumulative effects, and coping with both factors is possible at the expense of an extra recruitment of the ECN. Finally, results also revealed a time-on-task effect, with a progressive reduction of the HbO2 signal in the ECN during the flight scenario, suggesting that these regions are sensitive to short term habituation to the tasks. Overall, fNIRS efficiently indexed mental load, stress, and practice effects.

PGC-1α regulates critical period onset/closure, mediating cortical plasticity.

Peroxisome proliferator-activated receptor PPARγ coactivator-α (PGC-1α) is concentrated in inhibitory interneurons and plays a vital role in neuropsychiatric diseases. We previously reported some characteristic features of schizophrenia (SZ) in GABAergic neuron-specific Pgc-1alpha knockout (KO) mice (Dlx5/6-Cre: Pgc-1alphaf/f). However, there is a fundamental gap in the molecular mechanism by which the Pgc-1alpha gene is involved in the neurobehavioral abnormalities of SZ. The loss of critical period (CP) triggers-maturations of parvalbumin interneurons (PVIs) and brakes-and the formation of perineuronal nets (PNNs) implicates mistimed trajectories during adult brain development. In this study, using the Pgc-1alpha KO mouse line, we investigated the association of Pgc-1alpha gene deletion with SZ-like behavioral deficits, PVI maturation, PNN integrity and synaptic ultrastructure. These findings suggest that Pgc-1alpha gene deletion resulted in a failure of CP onset and closure, thereby prolonging cortical plasticity timing. To determine whether the manipulation of the PNN structure is a potential method of altering neuronal plasticity, GM6001, a broad-spectrum matrix metalloproteinase (MMP)-inhibitor was applied. Here we confirmed that the treatment could effectively correct the CP plasticity window and ameliorate the synaptic ultrastructure in the Pgc-1alpha KO brain. Moreover, the intervention effect on neuronal plasticity was followed by the rescue of short-term habituation deficits and the mitigation of aberrant salience, which are some characteristic features of SZ. Taken collectively, these findings suggest that the role of PGC-1α in regulating cortical plasticity is mediated, at least partially, through the regulation of CP onset/closure. Strategically introduced reinforcement of molecular brakes may be a novel preventive therapy for psychiatric disorders associated with PGC-1α dysregulation.

Olfactive short-term habituation in children and young people with profound intellectual and multiple disabilities

BackgroundDespite its importance for learning, the existence of the habituation process and its characteristics in people with profound intellectual and multiple disabilities (PIMD) remains understudied. Habituation is, however, considered the simplest form of learning, and a significant neuroadaptive mechanism. Even though habituation occurs in all sensory modalities, the olfactory system is where it manifests itself very visibly. AimThis study explores the olfactory short-term habituation abilities of children and young people with PIMD. MethodTwenty children and young people with PIMD (7–18 years) were presented six times successively with a 30-second habituating olfactory stimulus. The interstimulus interval was 15 s. A new odour was presented on the seventh trial. The scenario was carried out two times with two pairs of stimuli. The participants’ head alignment duration on the odour was measured. ResultsSeventeen participants out of 20 manifested a decline in response, which reached about 50 % between the first and sixth presentation of the habituation odour. All habituators also showed a distinctive response when exposed to a novel odour. The participants who did not habituate showed a strong, non-fluctuating response to the stimulus throughout the presentations. Three participants only habituated to one of the two habituation stimuli. Conclusion and implicationsThe results raise theoretical, scientific, and practical issues. They question the factors explaining olfactory habituation mechanisms, namely the stimulus properties and the severity of impairment, reveal the need for points of comparison for interpreting this population’s responses, and point to the consequences of stimuli repetition and or variety in therapeutic or educational settings for these individuals’ learning and cognitive functioning.

Exploring behavioral phenotypes in a mouse model of fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders are one of the leading causes of developmental abnormalities worldwide. Maternal consumption of alcohol during pregnancy leads to a diverse range of cognitive and neurobehavioral deficits. Although moderate-to-heavy levels of prenatal alcohol exposure (PAE) have been associated with adverse offspring outcomes, there is limited data on the consequences of chronic low-level PAE. Here, we use a model of maternal voluntary alcohol consumption throughout gestation in a mouse model to investigate the effects of PAE on behavioral phenotypes during late adolescence and early adulthood in male and female offspring. Body composition was measured by dual-energy X-ray absorptiometry. Baseline behaviors, including feeding, drinking, and movement, were examined by performing home cage monitoring studies. The impact of PAE on motor function, motor skill learning, hyperactivity, acoustic reactivity, and sensorimotor gating was investigated by performing a battery of behavioral tests. PAE was found to be associated with altered body composition. No differences in overall movement, food, or water consumption were observed between control and PAE mice. Although PAE offspring of both sexes exhibited deficits in motor skill learning, no differences were observed in basic motor skills such as grip strength and motor coordination. PAE females exhibited a hyperactive phenotype in a novel environment. PAE mice exhibited increased reactivity to acoustic stimuli, and PAE females showed disrupted short-term habituation. Sensorimotor gating was not altered in PAE mice. Collectively, our data show that chronic low-level exposure to alcohol in utero results in behavioral impairments.

Memory recovery through gene therapy with a single chain antibody fragment selective for Aβ oligomers in a model of Alzheimer’s disease in rats

Strong evidence supports the hypothesis that synapse damage and memory impairment in early Alzheimer disease (AD) might be due to synaptic failure caused by amyloid beta oligomers (AβOs). We demonstrated the preclinical efficacy of a single-chain variable-fragment (scFv) antibody NUsc1 that selectively targets a subpopulation of AβOs; NUsc1 prevented AβO-induced inhibition of long-term potentiation in hippocampal slices and short-term memory impairment in mice. Since specific targeting of AβOs by NUsc1 may be a substantial improvement in target engagement and efficacy for AD therapy, we developed an adeno-associated virus (AAV) vector to drive neuronal expression of NUsc1 within the brain. AAV-NUsc1 rescued short-term memory (STM) for objects and congeners interaction in mice AD models. Purpose: In heterozygous McGill-R-Thy1-APP transgenic (Tg+/–) rat model of AD, progressive amyloid pathology is accompanied by cognitive impairment involving long-term memory (LTM) decline. LTM in a novel-object-recognition (NOR) task was impaired in 4-month-old (Tg+/–) male rats, suggesting that they are unable to form/evoke such discriminative memories. Hence, we investigated if AAV-NUsc1 treatment could rescued this memory. Methods: 10-12 weeks-old either Tg or wild type male rats were i.c.v. infused with AAV-NUsc1. Two months later, short-term exploratory behavior, habituation to an open field (OF), object discrimination and LTM for objects were assessed. Results: AAV-NUsc1 treated Tg rats were able to successfully perform the task 24 h after training, denoting recovery of LT discrimination capacity and LTM formation. Wild type rats successfully performed the task either treated or not with AAV-NUsc1. Also, exploration and short-term habituation to an open field was preserved in Tg+/– rats either treated or not. Conclusions: Our present and previous results suggest that AAV-NUsc1 represents a significant advance in gene therapy, supporting the feasibility of immunotherapy using viral vector-mediated NUsc1 gene delivery as a potential therapeutic approach in AD.

Glutamatergic dysfunction leads to a hyper-dopaminergic phenotype through deficits in short-term habituation: a mechanism for aberrant salience

Psychosis in disorders like schizophrenia is commonly associated with aberrant salience and elevated striatal dopamine. However, the underlying cause(s) of this hyper-dopaminergic state remain elusive. Various lines of evidence point to glutamatergic dysfunction and impairments in synaptic plasticity in the etiology of schizophrenia, including deficits associated with the GluA1 AMPAR subunit. GluA1 knockout (Gria1−/−) mice provide a model of impaired synaptic plasticity in schizophrenia and exhibit a selective deficit in a form of short-term memory which underlies short-term habituation. As such, these mice are unable to reduce attention to recently presented stimuli. In this study we used fast-scan cyclic voltammetry to measure phasic dopamine responses in the nucleus accumbens of Gria1−/− mice to determine whether this behavioral phenotype might be a key driver of a hyper-dopaminergic state. There was no effect of GluA1 deletion on electrically-evoked dopamine responses in anaesthetized mice, demonstrating normal endogenous release properties of dopamine neurons in Gria1−/− mice. Furthermore, dopamine signals were initially similar in Gria1−/− mice compared to controls in response to both sucrose rewards and neutral light stimuli. They were also equally sensitive to changes in the magnitude of delivered rewards. In contrast, however, these stimulus-evoked dopamine signals failed to habituate with repeated presentations in Gria1−/− mice, resulting in a task-relevant, hyper-dopaminergic phenotype. Thus, here we show that GluA1 dysfunction, resulting in impaired short-term habituation, is a key driver of enhanced striatal dopamine responses, which may be an important contributor to aberrant salience and psychosis in psychiatric disorders like schizophrenia.

Short-Term Habituation of Auditory N1 in Spoken Word-Forms Is Modulated by Phonological Information

Short-term auditory habituation is typically reflected by decreased but recoverable amplitudes of the N1 component of event-related potentials to repeated stimuli. It remains less well understood whether and how N1 habituation is modulated by the human cognition. The current study aims to further test for the potential modulatory roles of phonological information carried by spoken word-forms. Two phonological variables, namely lexicality (real versus pseudoword-form) and usage frequency (high versus low frequency), are considered and combined factorially, yielding four types of monosyllabic Mandarin spoken word-forms. Each type consists of 10 items (i.e., word-forms). The stimuli were passively presented to native Mandarin speakers in trains of five (S1–S5), while their EEG was recorded. The peak amplitudes of N1 to the same type of speech stimuli were calculated for each position by averaging the trains extracted from the EEG recording. Then, the N1 habituation was quantified for the two electrodes of interest (C3 and C4) in each repetitive presentation position (S2–S5). The results showed that the N1 habituation in low-frequency pseudo word-forms was consistently greater than in low-frequency real word-forms and high-frequency pseudo word-forms, respectively, at the fourth presentation (S4). The results suggest the first evidence that different types of phonological information (i.e., lexicality and usage frequency) modulate N1 habituation, interactively. Sensory filtering is proposed as a candidate mechanism for mediating between the processing of phonological information and the short-term habituation of auditory N1.

Bisphenol A Exposure Induces Sensory Processing Deficits in Larval Zebrafish during Neurodevelopment.

Because of their ex utero development, relatively simple nervous system, translucency, and availability of tools to investigate neural function, larval zebrafish are an exceptional model for understanding neurodevelopmental disorders and the consequences of environmental toxins. Furthermore, early in development, zebrafish larvae easily absorb chemicals from water, a significant advantage over methods required to expose developing organisms to chemical agents in utero. Bisphenol A (BPA) and BPA analogs are ubiquitous environmental toxins with known molecular consequences. All humans have measurable quantities of BPA in their bodies. Most concerning, the level of BPA exposure is correlated with neurodevelopmental difficulties in people. Given the importance of understanding the health-related effects of this common toxin, we have exploited the experimental advantages of the larval zebrafish model system to investigate the behavioral and anatomic effects of BPA exposure. We discovered that BPA exposure early in development leads to deficits in the processing of sensory information, as indicated by BPA’s effects on prepulse inhibition (PPI) and short-term habituation (STH) of the C-start reflex. We observed no changes in locomotion, thigmotaxis, and repetitive behaviors (circling). Despite changes in sensory processing, we detected no regional or whole-brain volume changes. Our results show that early BPA exposure can induce sensory processing deficits, as revealed by alterations in simple behaviors that are mediated by a well-defined neural circuit.

Prenatal ethanol exposure impairs sensory processing and habituation to visual stimuli, effects normalized by enrichment of postnatal environmental.

Individuals with fetal alcohol spectrum disorders (FASD) often show processing deficits in all sensory modalities. Using an operant light reinforcement model, we tested whether prenatal ethanol exposure (PE) alters operant responding to elicit a contingent sensory stimulus-light onset (turning on the light) and habituation to this behavior in rats. We also explored whether postnatal environmental enrichment could ameliorate PE-induced deficits. Pregnant Sprague Dawley rats were gavaged twice/day with 0 or 3g/kg/treatment ethanol (15% w/v) during gestational days 8-20, mimicking second-trimester heavy PE in humans. The offspring were reared in a standard housing condition or an enriched condition. Adult male and female offspring underwent an operant light reinforcement experiment with either a short-access or a long-access procedure. A dishabituation test was also conducted to characterize the habituation process. In the short-access procedure, PE led to increased operant responding to the contingent light onset in both sexes reared in the standard housing condition. Such an effect was not observed in rats reared in enriched conditions due to an overall decrease in responding. Moreover, rats reared in enriched conditions showed greater short-term habituation. In the long access procedure, PE rats showed increased responding and impaired long-term habituation. The long-access procedure facilitated both short-term and long-term habituation in control and PE rats. Prenatal ethanol exposure increases responding to contingent light onset and impairs the long-term habituation process. The PE-induced deficits were ameliorated by rearing in the enriched environment and increasing the duration and frequency of exposure to light onset. The PE-induced effects are like increased sensation-seeking, a subtype of sensory-processing deficit that is often observed in individuals with FASD. Our findings could inform a suitable animal model for investigating the underlying mechanisms and possible intervention strategies for sensory deficits in FASD.

Memristor-Based Circuit Design of Non Associative Learning Mechanism

Associative learning and memory are widely studied, but non associative learning is rarely discussed. A non associative learning circuit based on memristor is proposed in this paper, including habituation, sensitization, presynaptic facilitation, secondary habituation, long and short term habituation, cross habituation, long and short timescale habituation. Habituation and sensitization in non associative learning are achieved through memristive non-volatility and non-linearity, and presynaptic facilitation is also discussed. Long and short term habituation and secondary habituation are considered through the synaptic module and the voltage module. Cross habituation and long and short timescale habituation are introduced through the suppression module and synaptic module. The more realistic brain is simulated by artificial neural network through the study of non associative learning.

ERPs Studies of Short- and Long-Term Habituation in Humans: A Systematic Review

Habituation is a type of learning that consists of a decrease in the response to a repetitive stimulus. The traditional view is that habituation comprises two processes: a transitory one called short-term habituation (STH), promoted by stimulus presentations at short intervals, and a more durable one called long-term habituation (LTH), promoted by more spaced repetitions. Due to the importance of time in this distinction and in an attempt to elucidate its underlying mechanisms, several studies have sought to relate habituation to brain activity through the analysis of event-related potentials (ERPs). We performed a systematic review of studies on habituation of ERPs in humans using the PRISMA methodology. A total of 175 articles were evaluated for eligibility and 145 were included. Most of the studies focused on short-term effects, demonstrating habituation in a range of ERP components such as P50, P1, N1, P2, N2, and P3. These studies revealed that STH occurs with intervals ranging from 75 ms to 4 s with an optimal of 500 ms, but it does not with intervals greater than 10 s. There are also some studies showing that the P1, N1, P2, N2, and P3 components exhibit LTH with inter-stimulus intervals between 3 and 10 seconds, but the evidence is yet insufficient to establish a secure conclusion with respect to LTH. We propose that future studies should use a wider range of inter-stimulus intervals with tests of both short-and long-term habituation so that the specific neurophysiological components of each type of habituation could be determined.

Event-Related Neural Responses to Short Term Habituation of Visual Food and Non-Food Stimuli

Event-Related Neural Responses to Short Term Habituation of Visual Food and Non-Food Stimuli

GABAB Receptor Agonist R-Baclofen Reverses Altered Auditory Reactivity and Filtering in the Cntnap2 Knock-Out Rat.

Altered sensory information processing, and auditory processing, in particular, is a common impairment in individuals with autism spectrum disorder (ASD). One prominent hypothesis for the etiology of ASD is an imbalance between neuronal excitation and inhibition. The selective GABAB receptor agonist R-Baclofen has been shown previously to improve social deficits and repetitive behaviors in several mouse models for neurodevelopmental disorders including ASD, and its formulation Arbaclofen has been shown to ameliorate social avoidance symptoms in some individuals with ASD. The present study investigated whether R-Baclofen can remediate ASD-related altered sensory processing reliant on excitation/inhibition imbalance in the auditory brainstem. To assess a possible excitation/inhibition imbalance in the startle-mediating brainstem underlying ASD-like auditory-evoked behaviors, we detected and quantified brain amino acid levels in the nucleus reticularis pontis caudalis (PnC) of rats with a homozygous loss-of-function mutation in the ASD-linked gene Contactin-associated protein-like 2 (Cntnap2) and their wildtype (WT) littermates using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS). Abnormal behavioral read-outs of brainstem auditory signaling in Cntnap2 KO rats were accompanied by increased levels of GABA, glutamate, and glutamine in the PnC. We then compared the effect of R-Baclofen on behavioral read-outs of brainstem auditory signaling in Cntnap2 KO and WT rats. Auditory reactivity, sensory filtering, and sensorimotor gating were tested in form of acoustic startle response input-output functions, short-term habituation, and prepulse inhibition before and after acute administration of R-Baclofen (0.75, 1.5, and 3 mg/kg). Systemic R-Baclofen treatment improved disruptions in sensory filtering in Cntnap2 KO rats and suppressed exaggerated auditory startle responses, in particular to moderately loud sounds. Lower ASR thresholds in Cntnap2 KO rats were increased in a dose-dependent fashion, with the two higher doses bringing thresholds close to controls, whereas shorter ASR peak latencies at the threshold were further exacerbated. Impaired prepulse inhibition increased across various acoustic prepulse conditions after administration of R-Baclofen in Cntnap2 KO rats, whereas R-Baclofen did not affect prepulse inhibition in WT rats. Our findings suggest that GABAB receptor agonists may be useful for pharmacologically targeting multiple aspects of sensory processing disruptions involving neuronal excitation/inhibition imbalances in ASD.

Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells

A hypofunction of N-methyl-D-aspartate glutamate receptors (NMDARs) has been implicated in the pathogenesis of schizophrenia by clinical and rodent studies. However, to what extent NMDAR-hypofunction in distinct cell-types across the brain causes different symptoms of this disease is largely unknown. One pharmaco-resistant core symptom of schizophrenia is impaired working memory (WM). NMDARs have been suggested to mediate sustained firing in excitatory neurons of the prefrontal cortex (PFC) that might underlie WM storage. However, if NMDAR-hypofunction in prefrontal excitatory neurons may indeed entail WM impairments is unknown. We here investigated this question in mice, in which NMDARs were genetically-ablated in PFC excitatory cells. This cell type-selective NMDAR-hypofunction caused a specific deficit in a delayed-matching-to-position (DMTP) 5-choice-based operant WM task. In contrast, T-maze rewarded alternation and several psychological functions including attention, spatial short-term habituation, novelty-processing, motivation, sociability, impulsivity, and hedonic valuation remained unimpaired at the level of GluN1-hypofunction caused by our manipulation. Our data suggest that a hypofunction of NMDARs in prefrontal excitatory neurons may indeed cause WM impairments, but are possibly not accounting for most other deficits in schizophrenia.

Decreased social interaction in the RHA rat model of schizophrenia-relevant features: Modulation by neonatal handling

The Roman-Low (RLA) and High-Avoidance (RHA) rat strains have been bidirectionally selected and bred, respectively, for extremely poor vs. rapid acquisition of the two-way active avoidance task. Over 50 years of selective breeding have led to two strains displaying many differential specific phenotypes. While RLAs display anxious-related behaviours, RHA rats show impulsivity, and schizophrenia-like positive and cognitive symptoms or phenotypes.Neonatal handling (NH) is an environmental treatment with long-lasting anxiolytic-like and anti-stress effects. NH also reduces symptoms related to schizophrenia, such as pre-pulse inhibition (PPI) impairment and latent inhibition (LI) deficits, and improves spatial working memory and cognitive flexibility.The present work was aimed at exploring whether RHAs also display negative schizophrenia-like symptoms (or phenotypes), such as lowered preference for social interaction (i.e. asociality), and whether NH would reduce these deficits. To this aim, we evaluated naïve inbred RHA and RLA rats in a social interaction (SI) test after either long- or short-term habituation to the testing set up (studies 1–2). In Study 3 we tested untreated and NH-treated RHA and RLA rats in novel object exploration (NOE) and SI tests. Compared with RHAs, RLA rats displayed increased anxiety-related behaviours in the NOE (i.e. higher behavioural inhibition, lesser exploration of the novel object) and SI (i.e. higher levels of self-grooming) tests which were dramatically reduced by NH treatment, thus supporting the long-lasting anxiolytic-like effect of NH. Remarkably, RHA rats showed decreased social preference in the SI test compared with RLAs, evidencing that RHAs would present a relative asociality, which is thought to model some negative symptomatology (i.e. social withdrawal) of schizophrenia. NH increased absolute levels of social behaviour in both strains, but with a more marked effect in RHA rats, especially in the first 5 min of the SI test. Thus, it is hypothesized that, apart from its effects on anxiety-related behaviours, NH might have long-lasting positive effects on behavioural and neurobiological processes that are impaired in schizophrenia.

Single dose testosterone administration enhances novelty responsiveness and short-term habituation in healthy males

The role of testosterone in sensory perception suggests that testosterone likely regulates adaptive responses to sensory changes, including habituation to repeated events and responsiveness to novel events. To test this hypothesis, we investigated how testosterone modulates brain responses to rapid changes in sensory inputs. Using a double-blind, placebo-controlled, within-participant design, each participant received a single dose of either testosterone or placebo, and then completed a passive auditory oddball task in which infrequent deviant tones were embedded in a series of frequent standard tones. Analysis of novelty-evoked potentials revealed smaller Mismatch Negativity (MMN) responses, but larger P3a responses in the testosterone session than in the placebo session. This suggests testosterone attenuates MMN responses that are associated with pre-attentive novelty detection and enhances P3a responses that are associated with involuntary attentional orientation toward novelty. Along with the repetition of standard tones, P2 responses on the auditory evoked potentials became significantly attenuated in the testosterone session, but not in the placebo session. This suggests testosterone enhances short-term habituation of P2 responses to recurring sensory events, which has been associated with bottom-up attention allocation. Mediation analysis further revealed that the role of testosterone in promoting attentional orientation toward novelty could be explained by the influence it exerts on short-term habituation and pre-attentive novelty detection. Overall, testosterone facilitated involuntary attention switching—withdrawal of attention from repeated sensory events and orientation toward novel sensory events—at the cost of attenuated pre-attentive novelty detection. This finding provides insight into the interplay between endocrinology and involuntary attentional processes.

Sensory filtering disruption caused by poly I:C - Timing of exposure and other experimental considerations

Maternal immune activation (MIA) in response to infection during pregnancy has been linked through various epidemiological and preclinical studies to an increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia in exposed offspring. Sensory filtering disruptions occur in both of these disorders and are typically measured using the acoustic startle response in both humans and rodents. Our study focuses on characterizing the baseline reactivity, habituation and prepulse inhibition (PPI) of the acoustic startle response following exposure to MIA. We induced MIA using polyinosinic: polycytidylic acid (poly I:C) at gestational day (GD) 9.5 or 14.5, and we tested sensory filtering phenotypes in adolescent and adult offspring. Our results show that startle reactivity was robustly increased in adult GD9.5 but not GD14.5 poly I:C offspring. In contrast to some previous studies, we found no consistent changes in short-term habituation, long-term habituation or prepulse inhibition of startle. Our study highlights the importance of MIA exposure timing and discusses sensory filtering phenotypes as they relate to ASD, schizophrenia and the poly I:C MIA model. Moreover, we analyze and discuss the potential impact of between- and within-litter variability on behavioural findings in poly I:C studies.

Exposure to Auditory Feedback Delay while Speaking Induces Perceptual Habituation but does not Mitigate the Disruptive Effect of Delay on Speech Auditory-motor Learning

Perceiving the sensory consequences of our actions with a delay alters the interpretation of these afferent signals and impacts motor learning. For reaching movements, delayed visual feedback of hand position reduces the rate and extent of visuomotor adaptation, but substantial adaptation still occurs. Moreover, the detrimental effect of visual feedback delay on reach motor learning—selectively affecting its implicit component—can be mitigated by prior habituation to the delay. Auditory-motor learning for speech has been reported to be more sensitive to feedback delay, and it remains unknown whether habituation to auditory delay reduces its negative impact on learning. We investigated whether 30 min of exposure to auditory delay during speaking (a) affects the subjective perception of delay, and (b) mitigates its disruptive effect on speech auditory-motor learning. During a speech adaptation task with real-time perturbation of vowel spectral properties, participants heard this frequency-shifted feedback with no delay, 75 ms delay, or 115 ms delay. In the delay groups, 50% of participants had been exposed to the delay throughout a preceding 30-minute block of speaking whereas the remaining participants completed this block without delay. Although habituation minimized awareness of the delay, no improvement in adaptation to the spectral perturbation was observed. Thus, short-term habituation to auditory feedback delays is not effective in reducing the negative impact of delay on speech auditory-motor adaptation. Combined with previous findings, the strong negative effect of delay and the absence of an influence of delay awareness suggest the involvement of predominantly implicit learning mechanisms in speech.

A high-throughput assay for screening environmental pollutants and drugs impairing predator avoidance in Daphnia magna

This study addresses short-term habituation of the escape response in the aquatic crustacean Daphnia magna evoked by sudden changes in light intensity, using a high-throughput system. Daphnia magna exhibits a marked phototactic behaviour and swim away from light to avoid predation by fish. Currently, there is no information available on the habituation of this phototactic response. The Daphnia photomotor response assay (DPRA) measures the distance moved after a sudden increase in light intensity. Using DPRA, it is possible to determine not only the magnitude of the phototactic response, but also its habituation after repetitive cycles of light and darkness. The progressive reduction observed in response to a series of light stimuli in the proposed assay meet the criteria for habituation. Most cholinergic and serotonergic modulators enhanced photomotor responses and reduced habituation. Dopaminergic and histaminergic modulators also reduced habituation, whereas diazepam was the only compound that increased habituation. Imidacloprid, apomorphine, diphenhydramine, diazepam, and memantine decreased photomotor responses. Thus, the DPRA was also predictive in assessing the effects of neuroactive and neurotoxic environmental contaminants such as selective serotonin reuptake inhibitors, diazepam, organophosphorous, and neonicotinoid pesticides. We conclude that the proposed DPRA may be an effective screening tool for compounds that can impair predation avoidance behaviour in aquatic organisms.