Bilateral Dorsal Cochlear Nucleus Lesions Prevent Acoustic-Trauma Induced Tinnitus in an Animal Model

Animal experiments suggest that chronic tinnitus (“ringing in the ears”) may result from processes that overcompensate for lost afferent input. Abnormally elevated spontaneous neural activity has been found in the dorsal cochlear nucleus (DCN) of animals with psychophysical evidence of tinnitus. However, it has also been reported that DCN ablation fails to reduce established tinnitus. Since other auditory areas have been implicated in tinnitus, the role of the DCN is unresolved. The apparently conflicting electrophysiological and lesion data can be reconciled if the DCN serves as a necessary trigger zone rather than a chronic generator of tinnitus. The present experiment used lesion procedures identical to those that failed to decrease pre-existing tinnitus. The exception was that lesions were done prior to tinnitus induction. Young adult rats were trained and tested using a psychophysical procedure shown to detect tinnitus. Tinnitus was induced by a single unilateral high-level noise exposure. Consistent with the trigger hypothesis, bilateral dorsal DCN lesions made before high-level noise exposure prevented the development of tinnitus. A protective effect stemming from disruption of the afferent pathway could not explain the outcome because unilateral lesions ipsilateral to the noise exposure did not prevent tinnitus and unilateral lesions contralateral to the noise exposure actually exacerbated the tinnitus. The DCN trigger mechanism may involve plastic circuits that, through loss of inhibition, or upregulation of excitation, increase spontaneous neural output to rostral areas such as the inferior colliculus. The increased drive could produce persistent pathological changes in the rostral areas, such as high-frequency bursting and decreased interspike variance, that comprise the chronic tinnitus signal

Trap-nesting biology of an ectoparasitoid spider wasp, Auplopus subaurarius (Hymenoptera: Pompilidae): the importance of wooded environments for niche generalist species

Abstract The insect group is one of the most diverse on the planet and due to habitat degradation, many of these species are becoming extinct, leaving a lack of information on the basic biology of each one. In this study, previously unseen information about nesting biology is revealed in Auplopus subaurarius trap nests. This is a solitary ectoparasitoid spider wasp that nests in preexisting cavities. We used a trap-nesting methodology to sample A. subaurarius in two different sampling periods (2017/2018 and 2020/2021) in three types of environment (forest, grassland and Eucalyptus plantation). In our study, the A. subaurarius nest building was more frequent during the hottest months of the year (November to March), with its highest abundance found within natural forest areas and in Eucalyptus plantation than in grassland areas. In addition, the species had two development times: a short one (three months) and a delayed one (up to one year). Moreover, females were larger than males (weight and size) and the species’ sex ratio had a tendency toward female production. Auplopus subaurarius presented seven natural enemy species: Ceyxia longispina, Caenochrysis crotonis, Photochryptus sp.1, Photochryptus sp.2, Messatoporus sp., Ephuta icema and Sphaeropthalma sp. We emphasize the importance of wooded environments to maintain the A. subaurarius populations and their associated interactors, both spiders and natural enemies, as these environments can provide better life conditions than grassland areas. Furthermore, other solitary wasps that may have the same lifestyle of A. subaurarius can also be improved by natural forest conservation and by good silviculture plantation planning, which should consider ecological aspects of Atlantic Forest landscapes

Effects of dopamine D2/D3 receptor antagonism on human planning and spatial working memory

Psychopharmacological studies in humans suggest important roles for dopamine (DA) D2 receptors in human executive functions, such as cognitive planning and spatial working memory (SWM). However, studies that investigate an impairment of such functions using the selective DA D2/3 receptor antagonist sulpiride have yielded inconsistent results, perhaps because relatively low doses were used. We believe we report for the first time, the effects of a higher (800 mg p.o.) single dose of sulpiride as well as of genetic variation in the DA receptor D2 gene (DA receptor D2 Taq1A polymorphism), on planning and working memory. With 78 healthy male volunteers, we apply a between-groups, placebo-controlled design. We measure outcomes in the difficult versions of the Cambridge Neuropsychological Test Automated Battery One-Touch Stockings of Cambridge and the self-ordered SWM task. Volunteers in the sulpiride group showed significant impairments in planning accuracy and, for the more difficult problems, in SWM. Sulpiride administration speeded response latencies in the planning task on the most difficult problems. Volunteers with at least one copy of the minor allele (A1+) of the DA receptor D2 Taq1A polymorphism showed better SWM capacity, regardless of whether they received sulpiride or placebo. There were no effects on blood pressure, heart rate or subjective sedation. In sum, a higher single dose of sulpiride impairs SWM and executive planning functions, in a manner independent of the DA receptor D2 Taq1A polymorphism.This research work was funded by a Core Award from the Medical Research Council and the Wellcome Trust to the Behavioural and Clinical Neuroscience Institute (MRC Ref G1000183; WT Ref 093875/Z/10/Z). Also supported by a Wellcome Trust Senior Investigator Award (104631/Z/14/Z) awarded to TWR. CE was supported by the Swiss National Science Foundation (PA00P1_134135) and the Vienna Science and Technology Fund (WWTF VRG13-007)

Deficits in visuo-spatial working memory, inhibition and oculomotor control in boys with ADHD and their non-affected brothers.

Few studies have assessed visuo-spatial working memory and inhibition in attention-deficit/hyperactivity disorder (ADHD) by recording saccades and consequently little additional knowledge has been gathered on oculomotor functioning in ADHD. Moreover, this is the first study to report the performance of non-affected siblings of children with ADHD, which may shed light on the familiality of deficits. A total of 14 boys with ADHD, 18 non-affected brothers, and 15 control boys aged 7-14 years, were administered a memory-guided saccade task with delays of three and seven seconds. Familial deficits were found in accuracy of visuo-spatial working memory, percentage of anticipatory saccades, and tendency to overshoot saccades relative to controls. These findings suggest memory-guided saccade deficits may relate to a familial predisposition for ADHD

Prefrontal dopamine and the dynamic control of human long-term memory

Dopaminergic projections to the prefrontal cortex support higher-order cognitive functions, and are critically involved in many psychiatric disorders that involve memory deficits, including schizophrenia. The role of prefrontal dopamine in long-term memory, however, is still unclear. We used an imaging genetics approach to examine the hypothesis that dopamine availability in the prefrontal cortex selectively affects the ability to suppress interfering memories. Human participants were scanned via functional magnetic resonance imaging while practicing retrieval of previously studied target information in the face of interference from previously studied non-target information. This retrieval practice (RP) rendered the non-target information less retrievable on a later final test—a phenomenon known as retrieval-induced forgetting (RIF). In total, 54 participants were genotyped for the catechol-O-methyltransferase (COMT) Val108/158Met polymorphism. The COMT Val108/158Met genotype showed a selective and linear gene-dose effect on RIF, with the Met allele, which leads to higher prefrontal dopamine availability, being associated with greater RIF. Mirroring the behavioral pattern, the functional magnetic resonance imaging data revealed that Met allele carriers, compared with Val allele carriers, showed a greater response reduction in inhibitory control areas of the right inferior frontal cortex during RP, suggesting that they more efficiently reduced interference. These data support the hypothesis that the cortical dopaminergic system is centrally involved in the dynamic control of human long-term memory, supporting efficient remembering via the adaptive suppression of interfering memories

Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory

Effects of methylphenidate on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)

The aim of this study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on attention in rats as measured using the 5-choice-serial-reaction-time task (5CSRTT) and to investigate whether methylphenidate has effects on DSP4-treated rats. Methylphenidate is a noradrenaline and dopamine reuptake inhibitor and commonly used in the pharmacological treatment of individuals with attention deficit/hyperactivity disorder (ADHD). Wistar rats were trained in the 5CSRTT and treated with one of three doses of DSP4 or saline. Following the DSP4 treatment rats were injected with three doses of methylphenidate or saline and again tested in the 5CSRTT. The treatment with DSP4 caused a significant decline of performance in the number of correct responses and a decrease in response accuracy. A reduction in activity could also be observed. Whether or not the cognitive impairments are due to attention deficits or changes in explorative behaviour or activity remains to be investigated. The treatment with methylphenidate had no beneficial effect on the rats’ performance regardless of the DSP4 treatment. In the group without DSP4 treatment, methylphenidate led to a reduction in response accuracy and bidirectional effects in regard to parameters related to attention. These findings support the role of noradrenaline in modulating attention and call for further investigations concerning the effects of methylphenidate on attentional processes in rats

Acoustic Overexposure Increases the Expression of VGLUT-2 Mediated Projections from the Lateral Vestibular Nucleus to the Dorsal Cochlear Nucleus

The dorsal cochlear nucleus (DCN) is a first relay of the central auditory system as well as a site for integration of multimodal information. Vesicular glutamate transporters VGLUT-1 and VGLUT-2 selectively package glutamate into synaptic vesicles and are found to have different patterns of organization in the DCN. Whereas auditory nerve fibers predominantly co-label with VGLUT-1, somatosensory inputs predominantly co-label with VGLUT-2. Here, we used retrograde and anterograde transport of fluorescent conjugated dextran amine (DA) to demonstrate that the lateral vestibular nucleus (LVN) exhibits ipsilateral projections to both fusiform and deep layers of the rat DCN. Stimulating the LVN induced glutamatergic synaptic currents in fusiform cells and granule cell interneurones. We combined the dextran amine neuronal tracing method with immunohistochemistry and showed that labeled projections from the LVN are co-labeled with VGLUT-2 by contrast to VGLUT-1. Wistar rats were exposed to a loud single tone (15 kHz, 110 dB SPL) for 6 hours. Five days after acoustic overexposure, the level of expression of VGLUT-1 in the DCN was decreased whereas the level of expression of VGLUT-2 in the DCN was increased including terminals originating from the LVN. VGLUT-2 mediated projections from the LVN to the DCN are likely to play a role in the head position in response to sound. Amplification of VGLUT-2 expression after acoustic overexposure could be a compensatory mechanism from vestibular inputs in response to hearing loss and to a decrease of VGLUT-1 expression from auditory nerve fibers

Pattern Classification of Working Memory Networks Reveals Differential Effects of Methylphenidate, Atomoxetine, and Placebo in Healthy Volunteers

Stimulant and non-stimulant drugs can reduce symptoms of attention deficit/hyperactivity disorder (ADHD). The stimulant drug methylphenidate (MPH) and the non-stimulant drug atomoxetine (ATX) are both widely used for ADHD treatment, but their differential effects on human brain function remain unclear. We combined event-related fMRI with multivariate pattern recognition to characterize the effects of MPH and ATX in healthy volunteers performing a rewarded working memory (WM) task. The effects of MPH and ATX on WM were strongly dependent on their behavioral context. During non-rewarded trials, only MPH could be discriminated from placebo (PLC), with MPH producing a similar activation pattern to reward. During rewarded trials both drugs produced the opposite effect to reward, that is, attenuating WM networks and enhancing task-related deactivations (TRDs) in regions consistent with the default mode network (DMN). The drugs could be directly discriminated during the delay component of rewarded trials: MPH produced greater activity in WM networks and ATX produced greater activity in the DMN. Our data provide evidence that: (1) MPH and ATX have prominent effects during rewarded WM in task-activated and -deactivated networks; (2) during the delay component of rewarded trials, MPH and ATX have opposing effects on activated and deactivated networks: MPH enhances TRDs more than ATX, whereas ATX attenuates WM networks more than MPH; and (3) MPH mimics reward during encoding. Thus, interactions between drug effects and motivational state are crucial in defining the effects of MPH and ATX

Haloperidol differentially modulates prepulse inhibition and p50 suppression in healthy humans stratified for low and high gating levels

Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D2-like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebo-controlled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D2-like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance