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Decreased effective connectivity between insula and anterior cingulate cortex during a working memory task after prolonged sleep deprivation
LiweiZhangaYongcongShaobXueguangJincXiaopingCaidFengDuae
doi : 10.1016/j.bbr.2021.113263
Volume 409, 9 July 2021, 113263
Total sleep deprivation (TSD) causes a decline in almost all cognitive domains, especially working memory. However, we do not have a clear understanding of the degree working memory is impaired under prolonged TSD, nor do we know the underlying neurophysiological mechanism. In this study, we recorded EEG data from 64 subjects while they performed a working memory task during resting wakefulness, after 24 h TSD, and after 30 h TSD. ANOVA was used to verify performance differences between 24 h and 30 h TSD in working memory tasks: (1) reaction time and accuracy hit rates, (2) P200, N200, and P300 amplitude and latency in measurements of event-related potential, as well as (3) effective connectivity strength between brain areas associated with working memory. Compared to 24 h TSD, 30 h TSD significantly decreased accuracy hit rates and induced a larger N200 difference waveform. The effective connectivity analysis showed that 30 h TSD also decreased beta frequency in effective connection strength from the right insular lobe to the left anterior cingulate cortex (ACC). Effective connection from the left ventrolateral prefrontal cortex to the left dorsolateral prefrontal cortex increased in the match condition of the 2-back task. In conclusion, 30 h TSD had a greater negative impact on working memory than 24 h TSD. This impairment of working memory is associated with decreased strength in the effective connection from the right insula to the left ACC.
Synergistic enhancing-memory effect of D-serine and RU360, a mitochondrial calcium uniporter blocker in rat model of Alzheimer's disease
ZeynabNiksereshtabcNematollahAhangardMahshidBadrikoohiabcParvinBabaeicab
doi : 10.1016/j.bbr.2021.113307
Volume 409, 9 July 2021, 113307
Although Amyloid beta (A?) and N - methyl d- aspartate receptors (NMDARs are involved in Ca2+ neurotoxicity, the function of mitochondrial calcium uniporter in cognition deficit remain uncertain. Here, we examined the effect of mitochondrial calcium uniporter (MCU) blocker, together with NMDA receptor agonist d-cycloserine (DCS) on memory impairment in a rat model of AD.
Fluoxetine tunes the abnormal hippocampal oscillations in association with cognitive impairments in 6-OHDA lesioned rats
WeitangLiuRenxingZhangHuFengHongyanZhu
doi : 10.1016/j.bbr.2021.113314
Volume 409, 9 July 2021, 113314
Cognitive decline is a common clinical symptom in Parkinson’s disease (PD) patients. Fluoxetine (FLU), a selective serotonin reuptake inhibitor, can improve cognitive deficits in demented patients. The present study investigated the effects of FLU on spatial learning and memory cognitions in 6-OHDA lesioned rats. Morris water maze (MWM) test showed that FLU significantly improved spatial cognitive deficits in rats with unilateral 6-OHDA injection at 4 and 7 weeks after 6-OHDA injection. Electrophysiological recordings demonstrated that the number and duration of high voltage spindles(HVSs)in the ipsilateral hippocampus of 6-OHDA lesioned rats were decreased by the administration of FLU. Furthermore, the spectral analysis of per frequency revealed increases in ? and ? rhythm power and decreases in ?, ? and ? rhythm power in the ipsilateral hippocampus of 6-OHDA lesioned rats in contrast to the saline-treated rats. Acute FLU treatment can reduce ? and ? rhythm power, and enhance ?, ? and ? rhythm power in the ipsilateral hippocampus of 6-OHDA lesioned rats. These findings suggest that FLU improves impaired cognition by tuning oscillatory activities in the hippocampus of 6-OHDA lesioned rats.
Decoding route selection of pigeon during goal-directed behavior: A joint spike-LFP study
ShuguanChengab1MengmengLiab1JiantaoFanabZhigangShangabHongWanab
doi : 10.1016/j.bbr.2021.113289
Volume 409, 9 July 2021, 113289
How to reach the goal is one of the core problems that animals must solve to complete goal-directed behavior. Studies have proved the important role of hippocampus (Hp) in spatial navigation and shown that hippocampal neural activities can represent the current location and goal location. However, for the different routes linking these two locations, the neural representation mechanism of the route selection in Hp is not clear. Here, we addressed this question using neural recordings of Hp ensembles and decoding analyses in pigeons performing a goal-directed route selection task known to require Hp participation. The hippocampal spike trains and local field potentials (LFPs) of five pigeons performing the task were acquired and analyzed. We found that the neuron firing rates and power spectrum characteristics in Hp could encode the animal’s route selection during goal-directed behavior, suggesting that the representation of route selection was coherent for hippocampal spike and LFP signals. Decoding results further indicated that joint spike-LFP features resulted in a significant improvement in the representation accuracy of the route selection. These findings of this study will help to understand the encoding mechanism of route selection in goal-directed behavior.
Pairing of neonatal phencyclidine exposure and acute adolescent stress in male rats as a novel developmental model of schizophrenia
Alexander A.MoghadamaLinnea R.VoseaOmidMirybXiao-LeiZhangaPatric K.Stantona
doi : 10.1016/j.bbr.2021.113308
Volume 409, 9 July 2021, 113308
Improved understanding of the neurophysiological and neurochemical mechanisms underlying schizophrenia is essential for the identification of biological markers and developing new therapeutic targets. The development of behaviorally faithful, predictive animal models is crucial to this endeavor. We have developed a novel two-hit paradigm designed to recapitulate in rodents the developmental process leading to appearance of human schizophrenia symptomatology. The model pairs neonatal administration of the NMDA receptor (NMDAR) open-channel blocker phencyclidine (PCP 10?mg/kg) to male rats at 7, 9 and 11 days of age, with later adolescent exposure (34 days of age) to a single prolonged stress paradigm consisting of 2?h restraint, followed by 20?min of forced swimming. Four experimental groups were examined: vehicle and no stress (VEH-NS), vehicle plus stress (VEH-S), PCP and no stress (PCP-NS), and PCP plus stress (PCP-S). Only pairing of neonatal PCP with single prolonged adolescent stress caused deficits in novel object recognition memory and increased anxiety-like behavior in the elevated plus maze task, without altering locomotor activity. In a separate cohort of animals, the PCP-S group showed significant reduction in magnitude of hippocampal long-term potentiation (LTP) at Schaffer collateral-CA1 synapses following a single pair of theta-burst stimuli (TBS), while LTP was diminished in both PCP treated groups when elicited by a second pair of TBS. These results suggest that the combination of neonatal PCP and acute adolescent stress are necessary for lasting cognitive impairment and anxiety-like phenotype, and that these behavioral impairments may be due to deficits in LTP in hippocampus, and perhaps elsewhere in the brain.
The bullies are the leaders of the next generation: Inherited aminergic neurotransmitter system changes in socially dominant zebrafish, Danio rerio
MariaSundvikHenriPuttonenSvetlanaSemenovaPerttiPanula
doi : 10.1016/j.bbr.2021.113309
Volume 409, 9 July 2021, 113309
We studied the social hierarchy in zebrafish and assessed differences in neurotransmitters and behavior in the F1 generation offspring of dominant and subordinate zebrafish (Danio rerio). We used behavioral assays to study locomotion, ability to complete cognitive tasks, social interaction and aggression. To study the neurochemical changes, we applied quantitative polymerase chain reaction, high pressure liquid chromatography and immunohistochemistry. Social hierarchies were formed both by males and females when animals were kept in same sex pairs in the dyadic dominant-subordinate hierarchy test. The offspring of dominant animals were the leaders in social interactions, however aggression in the mirror-test was not altered in any group. Serotonin and noradrenaline levels were lower in the F1 generation subordinate animals when compared with dominant animals, but not compared with animals that were naïve to social hierarchy. The mRNA level of the rate-limiting enzyme in histamine synthesis, histidine decarboxylase, was significantly lower in dominant and subordinate larval zebrafish when compared with control animals. In the dominant adult zebrafish tyrosine hydroxylase 1 mRNA level was lower compared with control animals, whereas tyrosine hydroxylase 2 mRNA was not different. The result was verified with immunohistochemistry. There were gender specific differences between the dominant and subordinate animals, where the dominant females performed better in cognitive tasks such as the T-maze than subordinate females. This was not observed in males, as the behavior of the dominant and subordinate males did not differ. These results add to the understanding of the plastic nature of the central nervous system and show that neurochemical features in aminergic neurotransmitter systems are associated with social leadership and dominance.
Altered resting-state functional connectivity of the default mode and central executive networks following cognitive processing therapy for PTSD
Tessa C.VuperCarissa L.PhilippiSteven E.Bruce
doi : 10.1016/j.bbr.2021.113312
Volume 409, 9 July 2021, 113312
Psychotherapy research is increasingly targeting both psychological and neurobiological mechanisms of therapeutic change. This trend is evident in and applicable to post-traumatic stress disorder (PTSD) treatment research given the high nonresponse rate of individuals with PTSD who undergo cognitive-behavioral therapy (CBT). Functional connectivity analyses investigating disrupted brain networks across mental disorders have been employed to understand both mental disorder symptoms and therapeutic mechanisms. However, few studies have examined pre-post CBT brain changes in PTSD using functional connectivity analyses. The current study investigated a) whether brain networks commonly implicated in psychopathology (e.g., default mode network [DMN], central executive network [CEN], and salience network [SN]) changed following Cognitive Processing Therapy (CPT) for PTSD and b) whether change in these networks was associated with PTSD and/or transdiagnostic symptom change. Independent components analysis was implemented to investigate resting-state functional connectivity in DMN, CEN, and SN in 42 women with PTSD and 18 trauma-exposed controls (TEC). Results indicated decreased CEN-cerebellum connectivity in PTSD participants versus TEC prior to CPT and decreased DMN connectivity in PTSD participants after CPT. Additionally, DMN and SN connectivity was related to change in positive and negative affectivity, while exploratory analyses at a cluster threshold of pFDR < .10 indicated DMN and SN connectivity was also related to change in PTSD symptoms and rumination. These findings provide evidence for normalization of CEN connectivity with treatment and implicate the DMN and SN in clinical symptom change following CPT.
The effect of GABA-B receptors in the basolateral amygdala on passive avoidance memory impairment induced by MK-801 in rats
MitraKhakpooracSalarVaseghibcMohammad-HosseinMohammadi-Mahdiabadi-HasanidMohammadNasehib
doi : 10.1016/j.bbr.2021.113313
Volume 409, 9 July 2021, 113313
MK-801 (dizocilpine) is a potent non-competitive N-methyl-[D]-aspartate (NMDA) receptor antagonist that affects cognitive function, learning, and memory. As we know, NMDA receptors are significantly involved in memory function, as well as GABA (Gamma-Aminobutyric acid) receptors. In this study, we aimed to discover the effect of GABA-B receptors in the basolateral amygdala (BLA) on MK-801-induced memory impairment. We used 160 male Wistar rats. The shuttle box was used to evaluate passive avoidance memory and locomotion apparatus was used to evaluate locomotor activity. MK-801 (0.125, 0.25, and 0.5??g/rat), baclofen (GABA-B agonist, 0.0001, 0.001, and 0.01??g/rat) and phaclofen (GABA-B antagonist, 0.0001, 0.001, and 0.01??g/rat) were injected intra-BLA, after the training. The results showed that MK-801 at the dose of 0.5??g/rat, baclofen at the doses of 0.001 and 0.01??g/rat, and phaclofen at the doses of 0.001 and 0.01??g/rat, impaired passive avoidance memory. Locomotor activity did not alter in all groups. Furthermore, the subthreshold dose of both baclofen (0.0001??g/rat) and phaclofen (0.0001??g/rat) restored the impairment effect of MK-801 (0.5??g/rat) on memory. Also, both baclofen (0.0001??g/rat) potentiated the impairment effect of MK-801 (0.125??g/rat) and phaclofen (0.0001??g/rat) potentiated the impairment effect of MK-801 (0.125 and 0.25??g/rat) on passive avoidance memory. In conclusion, our results indicated that BLA GABA-B receptors can alter the effect of NMDA inactivation on passive avoidance memory.
Effect of NEUROG3 polymorphism rs144643855 on regional spontaneous brain activity in major depressive disorder
ZhuoliangHoua1XiaoyunLiua1WenhaoJiangbZhenghuaHouaYingyingYinaChunmingXiecdHaisanZhangeHongxingZhangfZhijunZhangcdYongguiYuanad
doi : 10.1016/j.bbr.2021.113310
Volume 409, 9 July 2021, 113310
Our previous study identified a significant association between a single nucleotide polymorphism (SNP) located in the neurogenin3 (NEUROG3) gene and post-stroke depression (PSD) in Chinese populations. The present work explores whether polymorphism rs144643855 affects regional brain activity and clinical phenotypes in major depressive disorder (MDD).
Hyperhomocysteinemia increases susceptibility to cortical spreading depression associated with photophobia, mechanical allodynia, and anxiety in rats
ElenaGerasimovaaGulshatBurkhanovabKseniyaChernovabAndreyZakharovcbDanielEnikeevaNailKhaertdinovaRashidGiniatullinbdGuzelSitdikovaa
doi : 10.1016/j.bbr.2021.113324
Volume 409, 9 July 2021, 113324
Epidemiological data suggest that elevated homocysteine is associated with migraine with aura. However, how homocysteine contributes to migraine is still unclear. Here, we tested whether hyperhomocysteinemia (hHCY) promotes cortical spreading depression (CSD), a phenomenon underlying migraine with aura, and whether hHCY contributes to pain behavior. hHCY was induced by dietary methionine in female rats while the testing was performed on their 6–8week-old offspring. CSD and multiple unit activity (MUA) induced by KCl were recorded from the primary somatosensory cortex, S1, using multichannel electrodes. In hHCY rats, compared to control, we found: i) higher probability of CSD occurrence; ii) induction of CSD by lower concentrations of KCl; iii) faster horizontal propagation of CSD; iv) smaller CSD with longer duration; v) higher frequency of MUA at CSD onset along with slower reappearance. Rats with hHCY demonstrated high level of locomotor activity and grooming while spent less time in the central area of the open field, indicating anxiety. These animals showed light sensitivity and facial mechanical allodinia. Thus, hHCY acquired at birth promotes multiple features of migraine such as higher cortical excitability, mechanical allodynia, photophobia, and anxiety. Our results provide the first experimental explanation for the higher occurrence of migraine with aura in patients with hHCY.
Imbalance between dopamine and serotonin caused by neonatal habenula lesion
Young-ALeea1Yu-JeongKimab1Ju SungLeecSanghyunLeecYukioriGotod
doi : 10.1016/j.bbr.2021.113316
Volume 409, 9 July 2021, 113316
Alterations in dopamine (DA) and serotonin (5-HT) transmission have been implicated in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). We have previously reported that juvenile rats with neonatal habenula lesion (NHL) exhibit an assortment of behavioral alterations resembling ADHD symptoms. In this study, we investigated the impacts of NHL on DA and 5-HT transmission in mesocorticolimbic regions of rats. Male Sprague-Dawley rats with microinjection of ibotenic acid into the habenula at postnatal day (PND) 7 were subjected for a battery of locomotion test, object exploration test and delay discounting test in the juvenile period (PND28-35), followed by DA and 5-HT brain tissue concentration measurements using high-performance liquid chromatography (HPLC). NHL rats exhibited hyperlocomotion, impulsivity, and attention deficits. NHL induced alterations of tissue DA and 5-HT concentrations only in some mesocorticolimbic regions. However, positive correlations, indicating the balance, between DA and 5-HT observed in control (CTR) rats, were more extensively disrupted across mesocorticolimbic regions in NHL rats. Pharmacological manipulations that modulated both DA and 5-HT systems simultaneously with Astragalus membranaceus (AM) and its active compound formononetin (FOR) normalized the NHL-induced DA and 5-HT imbalance in several brain areas, which consequently improved the behavioral alterations. These results suggest that behavioral alterations caused by NHL may be associated with mesocorticolimbic DA/5-HT imbalance. Drug treatments targeting multiple monoamine systems may be useful to improve the NHL-induced changes.
Common variants of the autism-associated CNTNAP2 gene contribute to the modulatory effect of social function mediated by temporal cortex
DandanLiabce1LongZhangabc1TongjianBaiabc1WanlingHuangaGong-JunJiabceTingtingYangeYifanZhangeYanghuaTianabcBenshengQiudKaiWangabcef
doi : 10.1016/j.bbr.2021.113319
Volume 409, 9 July 2021, 113319
Autistic traits are highly heritable and characterized by social deficits. Common genetic variants of the autism-related CNTNAP2 gene have been linked with social impairments, but the neural substrates are poorly understood. In the present study, we investigated the genetic effect of common variants of CNTNAP2 (rs2710102 and rs7794745) on gray matter volume and its association with social performance among 442 healthy participants. Our results showed that individuals with rs2710102 GG homozygotes had smaller left superior temporal gyrus (STG)/insular volume than A-allele carriers (AA and AG), while individuals with rs7794745 TT and AT showed smaller right parahippocampal, right STG/insular, and left inferior parietal lobule (IPL) cortex volume than those with rs7794745 AA. Smaller volume of the STG/insular and parahippocampal cortex was associated with poorer social performance. An indirect effect of CNTNAP2 rs7794745 and rs2710102 genotype on the social performance was mediated by the STG/insular cortex and parahippocampal cortex volume. These findings provided insight into the genetic effect of CNTNAP2 variants on social behavior, which may be moderated by the temporal cortex.
Multiple cholinesterase inhibitors have antidepressant-like properties in the mouse forced swim test
Paul J.FitzgeraldPho J.HaleAnjeshGhimireBrendon O.Watson
doi : 10.1016/j.bbr.2021.113323
Volume 409, 9 July 2021, 113323
There is high clinical interest in improving the pharmacological treatment of individuals with Major Depressive Disorder (MDD). This neuropsychiatric disorder continues to cause significant morbidity and mortality worldwide, where existing pharmaceutical treatments such as selective serotonin reuptake inhibitors often have limited efficacy. In a recent publication, we demonstrated an antidepressant-like role for the acetylcholinesterase inhibitor (AChEI) donepezil in the C57BL/6J mouse forced swim test (FST). Those data added to a limited literature in rodents and human subjects which suggests AChEIs have antidepressant properties, but added the novel finding that donepezil only showed antidepressant-like properties at lower doses (0.02, 0.2 mg/kg). At a high dose (2.0 mg/kg), donepezil tended to promote depression-like behavior, suggesting a u-shaped dose-response curve for FST immobility. Here we investigate the effects of three other AChEIs with varying molecular structures: galantamine, physostigmine, and rivastigmine, to test whether they also exhibit antidepressant-like effects in the FST. We find that these drugs do exhibit therapeutic-like effects at low but not high doses, albeit at lower doses for physostigmine. Further, we find that their antidepressant-like effects are not mediated by generalized hyperactivity in the novel open field test, and are also not accompanied by anxiolytic-like properties. These data further support the hypothesis that acetylcholine has a u-shaped dose-response relationship with immobility in the C57BL/6J mouse FST, and provide a rationale for more thoroughly investigating whether reversible AChEIs as a class can be repurposed for the treatment of MDD in human subjects.
Optimization of behavioral testing in a long-term rat model of hypoxic ischemic brain injury
Tayla R.PennyabYenPhamaAmy E.SutherlandaMadeleine J.SmithabJoohyungLeecGrahamJenkinabMichael C.FaheydSuzanne L.MillerabCourtney A.McDonalda
doi : 10.1016/j.bbr.2021.113322
Volume 409, 9 July 2021, 113322
Hypoxic ischemic (HI) brain injury is a significant cause of childhood neurological deficits. Preclinical rodent models are often used to study these deficits; however, no preclinical study has determined which behavioral tests are most appropriate for long-term follow up after neonatal HI.
Effects of caloric restriction on monoaminergic neurotransmission, peripheral hormones, and olfactory memory in aged rats
DivkaRojic-Becker1MartaPortero-Tresserra1MargaritaMart?-NicoloviusAnnaVale-Mart?nezGemmaGuillazo-Blanch
doi : 10.1016/j.bbr.2021.113328
Volume 409, 9 July 2021, 113328
Aging is associated with a reduced ability to identify and discriminate scents, and olfactory dysfunction has been linked to preclinical stages of neurodegenerative diseases in humans. Moreover, emerging evidence suggests that smell-driven behaviors are regulated by hormones like insulin or leptin, and by metabolic parameters like glucose, which in turn may influence monoaminergic neurotransmission in brain areas related to cognition. Several studies have suggested that dietary interventions like caloric restriction (CR) can mitigate the age-induced decline in memory by modifying metabolic parameters and brain monoaminergic levels. The present study explored the effects of CR on age-dependent olfactory memory deficits, as well as their relationship with peripheral leptin, insulin and glucose levels, and brain monoamines. To this end, aged rats (24-months-old) fed on a CR diet or with ad libitum access to food, and adult rats (3–4 months), were trained in an odor discrimination task (ODT). The peripheral plasma levels of insulin, leptin, and glucose, and of monoamines and metabolites/precursors in brain areas related to olfactory learning and memory processes, such as the striatum and frontal cortex (FC), were determined. The data obtained indicated that CR attenuated the age-dependent decline in olfactory sensitivity in old animals fed ad libitum, which was correlated with the performance in ODT retention trial, as well as with leptin plasma levels. CR enhanced dopamine levels in the striatum, while it attenuated the age-related decline in serotonin levels in the striatum and FC. Such findings support a positive effect of CR on age-dependent olfactory sensitivity decline and dysfunctions in brain monoamine levels.
Altered structural covariance of hippocampal subregions in patients with Alzheimer’s disease
TongpengChu1JianLi1ZhongshengZhangPeiyouGongKailiCheYunaLiGangZhangNingMao
doi : 10.1016/j.bbr.2021.113327
Volume 409, 9 July 2021, 113327
Different atrophy of hippocampus subregions is a valuable indicator of patients with Alzheimer’s disease (AD). To explore the relationship among the hippocampal subregions of patients with AD, altered gray matter structural covariance of hippocampal subregions in patients with AD was studied.
Altered functional connectivity between the nucleus basalis of Meynert and anterior cingulate cortex is associated with declined attentional performance after total sleep deprivation
JingQiabBo-ZhiLibYingZhangcBeiPandYu-HongGaoeHaoZhandYongLiufghiYong-CongShaojkXiZhangba
doi : 10.1016/j.bbr.2021.113321
Volume 409, 9 July 2021, 113321
Sleep deprivation can markedly influence vigilant attention. The nucleus basalis of Meynert (NBM), the main source of cholinergic projections to the cortex, plays an important role in wakefulness maintenance and attention control. However, the involvement of NBM in attentional impairments after total sleep deprivation (TSD) has yet to be established. The purpose of this study is to investigate the alterations in NBM functional connectivity and its association with the attentional performance following TSD.
Atypical neural processing during the execution of complex sensorimotor behavior in autism
Robin L.ShaferaMark H.LewisbKarl M.NewellcJames W.Bodfishad
doi : 10.1016/j.bbr.2021.113337
Volume 409, 9 July 2021, 113337
Stereotyped behavior is rhythmic, repetitive movement that is essentially invariant in form. Stereotypy is common in several clinical disorders, such as autism spectrum disorders (ASD), where it is considered maladaptive. However, it also occurs early in typical development (TD) where it is hypothesized to serve as the foundation on which complex, adaptive motor behavior develops. This transition from stereotyped to complex movement in TD is thought to be supported by sensorimotor integration. Stereotypy in clinical disorders may persist due to deficits in sensorimotor integration. The present study assessed whether differences in sensorimotor processing may limit the expression of complex motor behavior in individuals with ASD and contribute to the clinical stereotypy observed in this population. Adult participants with ASD and TD performed a computer-based stimulus-tracking task in the presence and absence of visual feedback. Electroencephalography was recorded during the task. Groups were compared on motor performance (root mean square error), motor complexity (sample entropy), and neural complexity (multiscale sample entropy of the electroencephalography signal) in the presence and absence of visual feedback. No group differences were found for motor performance or motor complexity. The ASD group demonstrated greater neural complexity and greater differences between feedback conditions than TD individuals, specifically in signals relevant to sensorimotor processing. Motor performance and motor complexity correlated with clinical stereotypy in the ASD group. These findings support the hypothesis that individuals with ASD have differences in sensorimotor processing when executing complex motor behavior and that stereotypy is associated with low motor complexity.
Repeated treatment with alpha 7 nicotinic acetylcholine receptor ligands enhances cognitive processes and stimulates Erk1/2 and Arc genes in rats
AgnieszkaPotasiewiczaAgataFaron-GoreckabPiotrPopikaAgnieszkaNikiforuka
doi : 10.1016/j.bbr.2021.113338
Volume 409, 9 July 2021, 113338
The ?7 nicotinic acetylcholine receptor (?7 nAChR) is a potential target for the treatment of cognitive decline in patients with schizophrenia, Alzheimer’s disease, and attention-deficit/hyperactivity disorder.
A novel closed-loop EEG-tDCS approach to promote responsiveness of patients in minimally conscious state: A study protocol
GéraldineMartensab1DavidIb??ez-Soriac1AliceBarraab1AureliSoria-FrischcAndreaPiarullidOliviaGosseriesabRicardoSalvadorcAndrésRojascMichael A.NitscheefEleniKroupicStevenLaureysab2GiulioRuffinic2AuroreThibautab2
doi : 10.1016/j.bbr.2021.113311
Volume 409, 9 July 2021, 113311
Transcranial direct current stimulation (tDCS) applied over the prefrontal cortex has been shown to improve behavioral responsiveness in patients with disorders of consciousness following severe brain injury, especially those in minimally conscious state (MCS). However, one potential barrier of clinical response to tDCS is the timing of stimulation with regard to the fluctuations of vigilance that characterize this population. Indeed, a previous study showed that the vigilance of MCS patients has periodic average cycles of 70?min (range 57?80?min), potentially preventing them to be in an optimal neural state to benefit from tDCS when applied randomly. To tackle this issue, we propose a new protocol to optimize the application of tDCS by selectively stimulating at high and low vigilance states. Electroencephalography (EEG) real-time spectral entropy will be used as a marker of vigilance and to trigger tDCS, in a closed-loop fashion. We will conduct a randomized controlled crossover clinical trial on 16 patients in prolonged MCS who will undergo three EEG-tDCS sessions 5 days apart (1. tDCS applied at high vigilance; 2. tDCS applied at low vigilance; 3. tDCS applied at a random moment). Behavioral effects will be assessed using the Coma Recovery Scale-Revised at baseline and right after the stimulations. EEG will be recorded throughout the session and for 30?min after the end of the stimulation. This unique and novel approach will provide patients’ tailored treatment options, currently lacking in the field of disorders of consciousness.
Effect of hippocampal 6-OHDA lesions on the contextual modulation of taste recognition memory
Alejandro BorjaGrau-PeralesFernandoG?mizMilagrosGallo
doi : 10.1016/j.bbr.2021.113320
Volume 409, 9 July 2021, 113320
Taste recognition memory is evident in rodents because the initial neophobia to novel tastes attenuates across exposures as the taste becomes familiar and safe. This attenuation of taste neophobia (AN) is context-dependent and an auditory background change could induce the recovery of the neophobic response. The AN auditory context-dependency requires the hippocampal integrity but the neurochemical mechanisms underlying the interaction with the taste memory circuit remain unexplored. We have applied pharmacological intervention by 6-hidroxydopamine (6-OHDA) hippocampal lesion for assessing the role of catecholamines in the hippocampal system to Wistar rats that drank a novel 3% vinegar solution for several consecutive days. Additionally, we manipulated the auditory background as a context that could either change or remain constant across all the drinking sessions. We found that a disruption of the context-dependent AN was induced by intracerebral administration of 6-OHDA targeted to the ventral CA1 hippocampus (vCA1). We conclude that the ability of the auditory context to modulate taste recognition memory involves the catecholaminergic activity in the ventral hippocampal circuit for the proper acquisition of safe taste memory.
The effects of strain and estrous cycle on heroin- and sugar-maintained responding in female rats
Karl T.SchmidtJessica L.SharpSarah B.EthridgeTalliaPearsonShannonBallardKenzie M.PotterMark A.Smith
doi : 10.1016/j.bbr.2021.113329
Volume 409, 9 July 2021, 113329
Heroin intake decreases during the proestrus phase of the estrous cycle in female, Long-Evans rats. The purpose of this study was to (1) determine if proestrus-associated decreases in heroin intake extend across rat strains and (2) determine if proestrus-associated decreases in responding extend to a nondrug reinforcer. Female rats were implanted with intravenous catheters and trained to self-administer heroin. Estrous cycle was tracked daily for the duration of the study. During testing, Lewis, Sprague Dawley, and Long-Evans rats self-administered low (0.0025?mg/kg) and high (0.0075?mg /kg) doses of heroin and then self-administered sugar on fixed ratio (FR1) schedules of reinforcement. Heroin intake decreased significantly during proestrus in all three rat strains under at least one dose condition; however, sugar intake did not decrease during proestrus in any strain. These data suggest that responding maintained by heroin, but not a nondrug reinforcer, significantly decreases during proestrus in female rats and that these effects are consistent across rat strain.
Putative anxiolytic-like behavioral effects of acute paracetamol in adult zebrafish
Ana C.V.V.GiacominiabNaiaraScolariaLeticiaMarconaBarbara W.BuenoaBruna E.dos SantosaKonstantin A.DemincdijkAllan V.KalueffefiMurilo S.de Abreuagh
doi : 10.1016/j.bbr.2021.113293
Volume 409, 9 July 2021, 113293
Typically triggered by stress, anxiety disorders are most common and widespread mental illnesses. The zebrafish (Danio rerio) is rapidly becoming an important aquatic model species in stress research and central nervous system (CNS) drug screening. Paracetamol is currently the most prescribed medication for pain and fever, and is among the most used drugs globally. However, its CNS effects, especially on anxiety, in both clinical and animal studies remain poorly understood. Capitalizing on zebrafish as a powerful model system, here we evaluate the effects of paracetamol on anxiety-like behavior in adult fish, and its changes following an acute stress exposure. Overall, we report an anxiolytic-like profile of acute paracetamol treatment, and its alleviation of stress-evoked anxiety, in adult short-fin wild type zebrafish. Collectively, these findings suggest complex neuroactive effects of paracetamol, and reinforce the growing importance of zebrafish models for drug screening, including the search for novel putative anti-stress therapies.
New insights on nitric oxide: Focus on animal models of schizophrenia
Julio CésarMorales-MedinaaPatriciaAguilar-AlonsobAlessandroDi CerbocTommasoIannittidGonzaloFloresd
doi : 10.1016/j.bbr.2021.113304
Volume 409, 9 July 2021, 113304
Schizophrenia is a devastating complex disorder characterised by a constellation of behavioral deficits with the underlying mechanisms not fully known. Nitric oxide (NO) has emerged as a key signaling molecule implicated in schizophrenia. Three nitric oxide sinthases (NOS), endothelial, neuronal, and inducible, release NO within the cell. Animal models of schizophrenia are grouped in four groups, neurovedelopmental, glutamatergic, dopaminergic and genetic. In this review, we aim to evaluate changes in NO levels in animal models of schizophrenia and the resulting long-lasting behavioral and neural consequences. In particular, NO levels are substantially modified, region-specific, in various neurodevelopmental models, e.g. bilateral excitotoxic lesion of the ventral hippocampus (nVHL), maternal immune activation and direct NO manipulations early in development, among others. In regards to glutamatergic models of schizophrenia, phencyclidine (PCP) administration increases NO levels in the prefrontal cortex (PFC) and ventral hippocampus. As far as genetic models are concerned, neuronal NOS knock-out mice display schizophrenia-related behaviors. Administration of NO donors can reverse schizophrenia-related behavioral deficits. While most modifications in NO are derived from neuronal NOS, recent evidence indicates that PCP treatment increases NO from the inducible NOS isoform. From a pharmacological perspective, treatment with various antipsychotics including clozapine, haloperidol and risperidone normalize NO levels in the PFC as well as improve behavioral deficits in nVHL rats. NO induced from the neuronal and inducible NOS is relevant to schizophrenia and warrants further research.
Choose your path: Divergent basolateral amygdala efferents differentially mediate incentive motivation, flexibility and decision-making
Sara E.KeeferaUtsavGyawaliabDonna J.Caluab
doi : 10.1016/j.bbr.2021.113306
Volume 409, 9 July 2021, 113306
To survive in a complex environment, individuals form associations between environmental stimuli and rewards to organize and optimize reward seeking behaviors. The basolateral amygdala (BLA) uses these learned associations to inform decision-making processes. In this review, we describe functional projections between BLA and its cortical and striatal targets that promote learning and motivational processes central to decision-making. Specifically, we compare and contrast divergent projections from the BLA to the orbitofrontal (OFC) and to the nucleus accumbens (NAc) and examine the roles of these pathways in associative learning, value-guided decision-making, choice behaviors, as well as cue and context-driven drug seeking. Finally, we consider how these projections are involved in disorders of motivation, with a focus on Substance Use Disorder.
Functions of primate amygdala neurons in economic decisions and social decision simulation
FabianGrabenhorstWolframSchultz
doi : 10.1016/j.bbr.2021.113318
Volume 409, 9 July 2021, 113318
Long implicated in aversive processing, the amygdala is now recognized as a key component of the brain systems that process rewards. Beyond reward valuation, recent findings from single-neuron recordings in monkeys indicate that primate amygdala neurons also play an important role in decision-making. The reward value signals encoded by amygdala neurons constitute suitable inputs to economic decision processes by being sensitive to reward contingency, relative reward quantity and temporal reward structure. During reward-based decisions, individual amygdala neurons encode both the value inputs and corresponding choice outputs of economic decision processes. The presence of such value-to-choice transitions in single amygdala neurons, together with other well-defined signatures of decision computation, indicate that a decision mechanism may be implemented locally within the primate amygdala. During social observation, specific amygdala neurons spontaneously encode these decision signatures to predict the choices of social partners, suggesting neural simulation of the partner’s decision-making. The activity of these ‘simulation neurons’ could arise naturally from convergence between value neurons and social, self-other discriminating neurons. These findings identify single-neuron building blocks and computational architectures for decision-making and social behavior in the primate amygdala. An emerging understanding of the decision function of primate amygdala neurons can help identify potential vulnerabilities for amygdala dysfunction in human conditions afflicting social cognition and mental health.
