European Journal of Neuroscience

We report patch-clamp recordings from embryonic mouse olfactory sensory neurons that express the odorant receptor gene S1 or MOR23, using the odorous ligands 2-phenylethyl alcohol or lyral. We identify E16.5 as the upper limit of the acquisition of odorant responsiveness by these neuronal populations. The S1 and MOR23 glomeruli in the olfactory bulb are formed postnatally. These neuronal populations can thus respond to a cognate odorant several days before their axons coalesce into glomeruli.

Prenatal nicotine exposure has been associated with many negative outcomes including increased risk for nicotine addiction in adulthood. In this study we examined neuroanatomical changes that occurred in response to nicotine exposure in the prenatal period and in adolescence. Although combined exposure to nicotine at both time points was rarely additive; nicotine administration in adolescence profoundly altered neuronal morphology and synaptic plasticity in the brain regions examined.

Participants performed a simulated air traffic control task for two hours, while their eye movements were measured. Microsaccadic velocity decreased with time-on-task, whereas drift velocity increased, suggesting that ocular instability increases with mental fatigue.

In order to further investigate the influence of miniature saccades on gamma band oscillations, EEG and eye tracking were combined in a repetition priming task. Results show that miniature saccades are only sensitive to object familiarity, while artifact-corrected, ongoing gamma band oscillations were sensitive to object familiarity and object repetition. It is concluded that gamma band responses reflect cortical network activity whereas miniature saccades mirror early perceptual mechanisms.

We tested with MEG whether perceptual grouping affects the processing of sound omission in a tone sequence. Omission in a random tone sequence, compared to a regular tone sequence, elicited larger brain responses in both musicians and nonmusicians. However, the cortical activation pattern differed between them. This indicates that, depending on musical experience, different cortical areas might be implicated in the perceptual grouping of tone sequences.

Activation of the nucleus incertus by electrical stimulation, CRF infusion or stress is likely to attenuate medial prefrontal cortical activity and suppress hippocampo-medial prefrontal cortical LTP.

The bilateral microinjection of the CoCl₂ or LY235959 into the LH enhanced the HR increase evoked by restraint stress without affecting the blood pressure increase. Intravenous administration of the homatropine methyl bromide abolished the changes in cardiovascular responses to restraint stress following LH treatment with LY235959.

These results suggest that such LH influence is mediated by local NMDA glutamate receptors and involves parasympathetic nervous activation.

This study showed that, without reward prospect, saccadic peak velocity decreased linearly as initial eye position deviated in the direction of the saccade. However, with reward prospect, the slope (rate) and the intercept (magnitude) of the velocity bias was reduced and increased, respectively, with amplitude. The findings suggest that reward modulation was not an additive signal, but as a facilitating mechanism that interacted with the biomechanical regulation.

We have observed persistent neural activity following a step current injection (2 s, 100 pA or 200 ms, 100 pA) in hippocampal CA3 pyramidal cells under cholinergic stimulation. The persistent neural activity is independent of ionotropic synaptic transmission.

Neurotrophin systems are implicated in reward seeking. Here we show that Bdnf knockdown selectively in the orbitofrontal prefrontal cortex confers resistance to the extinction of cocaine-conditioned place preference.

A theory positing that sleep is initiated within small local neuronal networks is presented. Sleep-like states occur in small networks such as cortical columns and the biochemical events responsible include sleep regulatory substances. The activity-dependent local sleep mechanisms are associated with changes in receptor trafficking and provide an explanation for clinical phenomena such as sleep inertia and sleep disorders such as insomnia.

A phenotypically diverse population projects from the pressor region of the rostral ventrolateral medulla to its analogue in the contralateral brainstem. These neurons are spontaneously active, have a discharge correlated with sympathetic nerve activity, and form close appositions with sympathetic premotor neurons. These neurons may therefore represent a source of ongoing excitatory input to sympathetic premotor neurons.

The goal of the present review is to discuss our current understanding of the cellular and molecular mechanisms controlling the migration of cortical GABAergic interneurons, with an emphasis on those migrating to the neocortex. The data summarized here demonstrate that different mechanisms operate at distinct phases in the migration of interneurons from the subpallium to their final destination in the neocortex.

We describe the role of endogenous Protein Kinase A (PKA) signalling in vivo in shaping the population activity of respiratory neurons that regulate respiratory rhythm and motor patterns. We identify two key functions of PKA activity: (i) potentiating inspiratory drive currents of prebötzinger neurons and phrenic premotor neurons that regulate the intensity of phrenic nerve discharge, and (ii) potentiating glycinergic transmission that restrains the frequency of rhythmic respiratory activity.

Several commonly used therapeutic drugs target Cl⁻ permeable GABA_A receptors. In the current study, hyperexcitability caused by glutamate or by inhibition of KCC2 rapidly increased Cl⁻ levels inside neurons. This buildup reduced the ability of diazepam to suppress neuronal activity. However, the same conditions did not affect inhibition by propofol. Changes in intracellular Cl⁻ could therefore selectively impact the therapeutic efficacy of GABA_A modulators during specific pathological states.

We found that anti-CB₁ sera, in parallel to CB₁, also recognize the mitochondrial protein stomatin-like protein 2. In addition, we show that the previously reported effect of synthetic cannabinoid WIN 55,212-2 on mitochondrial complex III respiration is not detectable in purified mitochondrial preparations. Thus, our study indicates that a direct relationship between endocannabinoid signaling and mitochondrial functions in the cerebral cortex seems unlikely and that caution should be taken interpreting findings obtained using anti-CB₁ antibodies.

We showed a relationship between reward sensitivity trait and brain activity in the midbrain and the NAcc during reward anticipation. We have also showed reward sensitivity modulation on the connectivity of these areas with the mOFC and amygdala, respectively. Our results suggest that high reward sensitivity-related activations in reward brain areas may partially result from diminished modulatory effects of other regions of reward circuitry.

Previous evidence suggests a circadian modulation of drug-seeking behavior and responsiveness to drugs of abuse. To identify potential mechanisms for rhythmicity in reward, a maker of neural activation (cFos) was examined across the day in the mesolimbic reward system.

Immunocytochemistry shows that purinergic receptors A₁R and A_2AR are present in the nerve endings at the mouse neuromuscular junction. Electrophysiology in µ-CgTx-GIIIB paralyzed muscles show that the receptors might have no real effect on neuromuscular transmission in resting conditions. However, these receptors can conserve resources by limiting spontaneous quantal leak of ACh (mainly A₁Rs) and may protect synaptic function by reducing the magnitude of depression during repetitive activity.

Our findings provide a dual function of GJIC in the proliferation and neuronal differentiation of human progenitors, which is modulated by Cx43 expression. Strong cell- cell coupling, accompanied by high Cx43 expression, is required to maintain cells in a proliferative state. Decreased GJIC in the early stage of differentiation promotes neuronal differentiation, while a later re-increase of gap junctional coupling is important for the establishment of a dense neural network.

Syntenin-a is upregulated caudal to the lesion site following spinal cord injury in adult zebrafish. Knock-down syntenin-a expression by morpholino resulted in inhibition of locomotor recovery and regrowth of axons from brain. These observations indicate that syntenin-a is involved in central nervous system regeneration, potentially leading to novel insights into the cellular and molecular mechanisms that may be require activation in the regeneration-deficient mammalian central nervous system.

Male Syrian hamsters develop a conditioned place preference (CPP) for social interactions. However, as shown in Figs A & B, social status increases reward value. That is, the effects of conditioning on the development of a CPP are significantly greater for dominant males compared to their subordinate partners. Direct social interactions induce high levels of Fos-ir in the VTA when compared to less direct forms of social contact (i.e., exposure to a caged stimulus hamster) or no social stimulus (Figs C & D). In addition, high levels of neural activation in the VTA are associated with high levels of aggression and social dominance behaviors, and social experience modulates the response of the VTA to novel social stimuli. Therefore, our data suggest that the mesolimbic reward system may play a role in social reward.

Transgenic mice expressing GFP under the control of the ERα promoter has been generated. GFP-positive neurons were observed in areas previously reported to express ERα mRNA, and GFP signals mostly overlapped with ERα immunoreactivity. Targeting of ERα gene by adeno-associated virus-mediated small hairpin RNA expression induced GFP in the medial preoptic area, suggesting a negative feedback mechanism in which ERα controls expression of the ERα gene itself.

Alcohol abuse is a major health, economic and social concern in modern societies but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction.

To study the selectivity of the human visual system to spatial phase, we measured the BOLD response to modulation of luminance and chromatic stimuli differing only in phase spectra: highly congruent or random. Strong phase selectivity was observed for both luminance and color stimuli, along both dorsal and ventral pathways. V1 showed a balanced response to all stimuli, suggesting the existence of equal number of even- and odd- chromatic receptive fields.

The tremulous jaw movement (TJM) model was used to study the effects of subthalamic (STN) deep brain stimulation (DBS) in rats. STN DBS reduced the TJMs induced by dopamine antagonists and cholinomimetic drugs. The ability of DBS to suppress TJMs was dependent upon the neuroanatomical locus being stimulated, and the frequency and intensity of stimulation used. Administration of the adenosine A_2A receptor antagonist MSX-3 reduced the frequency and intensity parameters needed to reduce TJMs.

In this work, we studied the roles of Drosophila NOMPC in mechanotransduction. Here we report our findings that the previously reported NOMPC-dependent adapting mechanoreceptor current (MRC) responses in external bristle mechanosensory organs are chloride-dependent, and NOMPC is likely a key component of Drosophila mechanotransduction channels. These findings provide important clues toward understanding the mechanism of mechanosensation in the fruit fly.

In order to influence synaptic communication microglia move in the neuropil and contact synapses. By immunogold electron microscopy we here show that at a given time point direct interaction between microglia and synapses in the brain is rather infrequent. However, the most delicate microglial processes, which are the ones that contact synapses, are equipped with high levels of Iba1 and actin, enabling them to move in the neuropil.

In rats with many months of recovery periods following lesions of the dorsal funiculus of the spinal cord, the motor cortex undergoes large-scale reorganization such that the whiskers or the neck movement representations expand to completely reactivate the entire de-efferented motor cortex.

Using a rat model of ischemia (permanent middle cerebral artery occlusion; pMCAO) we demonstrate that whisker stimulation can completely protect the cortex from impending stroke. Furthermore, the broad extent of evoked activity evident under isoflurane anesthesia plays a significant role in the protection from, or deterioration towards infarct. We conclude that the pMCAO model may be carried out using isoflurane, allowing for the future investigation of ischemic stroke in awake animals.

Excitotoxicity is thought to be important in the pathogenesis of Huntington's disease (HD). Glutamate is the predominant excitatory neurotransmitter in the brain and excess activation of glutamate receptors can cause neuronal dysfunction and death. GLT-1 is the most abundant glutamate transporter, and here we show it is expressed in both excitatory terminals and astrocytes in the striatum. Our results suggest that changes in GLT-1 expression or function per se are unlikely to potentiate or ameliorate HD progression.

Converging lines of evidence point to the occipitotemporal cortex (OTC) as a critical structure in visual perception. For instance, human functional magnetic resonance imaging (fMRI) has revealed a modular organisation of object-, face-, body- and scene-selective visual areas in OTC and disruptions to the processing within these regions, either in neuropsychological patients or through transcranial magnetic stimulation (TMS), can produce category-specific deficits in visual recognition. In the present paper, Gallivan and colleagues show, using fMRI and pattern classification methods, that the activity in several areas of the OTC also represent how stimuli will be interacted with by the body – a level of processing more traditionally associated with the preparatory activity in sensorimotor circuits of the brain.

Early life experiences are crucial factors that shape brain development and function due to their ability to induce structural and functional plasticity. Among these experiences, early life stress (ELS) is known to interfere with brain development and maturation, increasing the risk of future psychopathologies, including depression, anxiety, and personality disorders.

Fluoxetine is a widely prescribed drug which is well known for its antidepressant activity by selective inhibition of recapture of serotonin in the brain. Using orientation tuning curve shifts as a model, we show that fluoxetine and serotonin facilitate attractive-adaptation-induced-orientation short-term plasticity in the primary visual cortex without modulating the firing rate of neurons.

Ablating the cochlea of adult rats causes a total sensory deafferentation of the cochlear nucleus. Degeneration of the auditory nerve and its synaptic terminals temporally overlaps with the formation of new synapses in the cochlear nucleus. We show that the process of establishing new synaptic contacts prompts astrocytes to recompose their molecular profile, indicating that they are an integral component of a lesion-induced re-organisation in the adult brain.

Methamphetamine (METH) neurotoxicity leads to long-term damage to brain dopamine (DA) systems. Here we demonstrate that METH-induced DA depletion causes deficits in phasic DA signaling, which is important to reward-based learning, in freely-moving rats. This is the first report identifying deficits in naturally occurring phasic DA signaling in any DA-denervation model, and these deficits may serve as a mechanistic link between DA depletion and cognitive impairments associated with METH abuse.

The IC microinjection of CoCl₂, either after the conditioning session or before the test session, attenuated the behavioral (freezing) and cardiovascular responses evoked by the re-exposure to an aversively conditioned context. However, the inactivation of the IC did not impair the acquisition of the contextual fear memory when CoCl₂ was microinjected before the conditioning session. These results suggest the involvement of IC in both the consolidation and expression of contextual fear memory.

The striatal decrease of dopamine increased the extracelular glutamate pool. The glutamatergic thalamo-striatal pathway degenerated with the striatal increase of glutamate. Present data in rats suggest that glutamatergic hyperactivity in the striatum could be the cause of a retrograde degeneration of the intralaminar thalamic nuclei in Parkinson's disease.

Obstructive sleep apnoea (OSA) causes changes within the brain that may affect intracortical inhibition (ICI) and neuroplasticity. We investigated this possibility using transcranial magnetic stimulation (TMS) in patients with severe OSA, where neuroplastic changes were induced using continuous theta-burst stimulation (cTBS). Patients showed normal ICI, but failed to respond to cTBS. These results suggest that motor cortex neuroplasticity is altered in OSA.

Injury of the CA1 subregion induced by a single injection of kainic acid (1×KA) is attenuated when juvenile animals (P20) have a history of two sustained neonatal seizures on P6 and P9. To identify gene candidates involved in the spatially protective effects produced by early life conditioning seizures we profiled and compared the transcriptomes of CA1 subregions from control, 1×KA, and 3×KA treated animals.

This study investigates the protective action on cones of a pharmacological treatment shown to prolong rod life. To this purpose, myriocin- loaded nanoparticles were delivered as eye drops in an animal model of Retinitis Pigmentosa. The immunocytochemical and the electrophysiological tests showing cone survival and inner retina preservation were confirmed by measuring the overall visual performance. These results may help to develop new therapeutic schemes for retinal degeneration in humans.

We analysed the effects of the schizophrenia-associated risk variant in AMBRA1 (rs11819869) on impulsivity-related traits on a behavioral, temperament, and neural level in a large sample of healthy adolescents. Our findings support the hypothesis that rs11819869 is involved in various aspects of impulsivity, and that this involvement occurs on a behavioral- as well as an imaging genetics level.

Tardive dyskinesia (TD) is a delayed and potentially irreversible motor complication arising in patients chronically exposed to antipsychotic drugs. As several modern (so-called atypical) antipsychotic drugs are common offenders, the widening clinical indications for prescription as well as exposure of vulnerable individuals, TD will remain a significant drug-induced unwanted side effect.

Eyeblink classical conditioning (EBCC) is a cerebellum-dependent paradigm of associative motor learning and abnormal EBCC is a neurophysiological indicator of cerebellar dysfunction. We have previously demonstrated impaired EBCC in patients with primary dystonia, but it remains uncertain if this represents actual cerebellar pathology or reflects a functional cerebellar disruption.

The major finding of our study is that D-cycloserine facilitates the fear extinction by enhancing synaptic plasticity in infralimbic prefrontal cortex and specific subnuclei in the amygdala, specifically the intercalated neurons and lateral subdivision of central amygdala. Our findings suggest that the efficacy of DCS in neuropsychiatric disorders may be partly due to its ability to selectively affect neuronal activity and signaling in the mPFC and amygdala subnuclei.

The presence of depression during rehabilitation from alcohol abuse is associated with a greater chance for relapse, raising the need for methods to prevent depression from developing. In this study, depression-related behaviours detected in mice during abstinence after chronic alcohol consumption are attenuated through engagement in wheel-running. This study supports the use of physical exercise as a simple, low-cost therapeutic intervention as part of a broader rehabilitative program for alcoholism.

We investigated whether eating or fear generated by GABA inhibition of accumbens shell depend on local dopamine, and whether the valence of these behaviors can be retuned by changes in environmental ambience, similarly to glutamate blockade. We report that the answer to both questions is ‘no’. These results suggest that GABA-induced motivated behaviors are both independent of modulatory dopamine signals and more anatomically pre-determined than the same behaviors elicited by glutamate blockade.

Neurophysiological recordings of single cells in monkey medial prefrontal cortex (mPFC) identified two cell populations whose mean firing rates altered significantly on eye-closure (sleep). The main finding is that Type 1 cells significantly increased their mean firing rate from 3.1 spikes/s when awake to 10.2 spikes/s when asleep (P«0.01). The data thus identify a substantial population of mPFC neurons (28% of total recorded cells) that increase their firing rates during periods of ‘eye-closure’ and sleep. This suggests that identified areas of monkey mPFC are part of the anterior ‘default mode network’.

Variation in dopamine receptor levels has been associated with different facets of impulsivity. To further delineate the neural substrates underlying impulsive action (inability to withhold a prepotent motor response) and impulsive choice (delay aversion), we characterised rats in the Differential Reinforcement of Low Rates of Responding task and a delay discounting task.

Horizontal images of body width were involved in the somatosensory areas, whereas dorsoventral images of thickness were associated with the left anterior fusiform gyrus. These results suggest neural dissociations between the two body axes: dorsoventral images of thickness may require visual processing, whereas bodily sensations are involved in horizontal body size perception.

The data demonstrate that mice are highly responsive to the sleep inducing properties of light early in the dark phase across a range of illuminances. The transition to sleep is characterised by a rapid induction, followed by a period of sleep maintenance, and ending with a rapid return to wake post pulse across light intensities and durations. We also find that the melanopsin expressing retinal ganglion cells in the retina are important for the long-term maintenance of light induced sleep.

We demonstrated that responses in the AC were substantially modulated during an auditory detection task and that these modulations were systematically related to top-down processes. Importantly, despite these significant modulations, the spectrotemporal receptive fields of all neurons remained remarkably stable.

Participants practiced a finger sequence task under either single- or dual-task (probe) condition. 1 Hz rTMS was delivered to either dPM or M1 after practice for the rTMS groups. Motor learning was assessed by computing forgetting, the performance difference between immediate retention (R1) and delayed retention (R2) tests. Dual-task practice led to less forgetting compared to single-task practice. rTMS to dPM but not M1 attenuated the benefit of dual-task practice.

The frontal eye fields (FEF), located in prefrontal cortex, participate in the transformation of visual signals to gaze motor commands. We stimulated the FEF in head-unrestrained monkeys to see whether this produces gaze shifts toward eye-fixed goals, or toward goals defined in other frames. Consistent with the FEF's intermediate placement within high-level gaze circuitry, we found that the frames for its motor output varied site-by-site, mainly within the continuum between eye and head frames.

We investigated voluntary, FES-assisted and FES-evoked movements with intact and abolished sensory processing during fMRI. We found that processing in S1, M1, S2, PMd, SMA and cerebellum only during FES-evoked movements was reduced as a consequence of abolished sensory processing. We found that processing in SPL only during voluntary movements was reduced as a consequence of abolished sensory processing.

White matter injury is common following traumatic brain injury and may lead to reduced functional connectivity and impaired cognitive function. In two widely used models of traumatic brain injury, axonal injury, demyelination, oligodendrocyte death and oligodendrocyte precursor changes were evaluated. Brain injury caused widespread demyelination and axon injury, accompanied by apoptotic oligodendrocytes and an increased number of oligodendrocyte progenitors in white matter tracts.

The neuronal Per-Arnt-Sim domain protein 4 (Npas4) is an important transcriptional regulator of synaptic plasticity and cognition. The present study characterises the in vivo neuroanatomical expression pattern of the Npas4 protein in a rat model of focal cerebral ischemia.

Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depression; mice lacking BDNF expression through promoter IV (BDNF-KIV) exhibit a depression-like phenotype. We tested our hypothesis that deficits caused by promoter IV deficiency—depression-like behavior, decreased levels of BDNF, and neurogenesis in the hippocampus (HIP)—could be rescued by 3-week treatment with different types of antidepressants: fluoxetine, phenelzine, duloxetine, or imipramine.