Hippocampal neural disinhibition, i.e. reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology. The hippocampus is an important part of the neural circuitry that controls fear conditioning and can also modulate prefrontal and striatal mechanisms, including dopamine signalling, which play a role in salience modulation. Consequently, hippocampal neural disinhibition may contribute to impairments in fear conditioning and salience modulation reported in schizophrenia. Therefore, we examined the effect of ventral hippocampus (VH) disinhibition in male rats on fear conditioning and salience modulation, as reflected by latent inhibition (LI), in a conditioned emotional response procedure (CER). A flashing light was used as the conditioned stimulus (CS) and conditioned suppression was used to index conditioned fear. In Experiment 1, VH disinhibition via infusion of the GABA-A receptor antagonist picrotoxin prior to CS pre-exposure and conditioning markedly reduced fear conditioning to both ...

The major pathology in Parkinson’s disease (PD) is neuron injury induced by degeneration of dopaminergic neurons and the activation of microglial cells. The objective of this study is to determine the effect and mechanism of miR-132-3p in regulating neuroinflammation and the degeneration of dopaminergic neuron in PD. The expressions of miR-132-3p in brain tissues of PD patients, lipopolysaccharide (LPS)-induced BV-2 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models were detected. The effect of miR-132-3p and GLRX in cell viability, apoptosis and inflammation was verified in BV-2 cells. The activation of Iba1 in substantia nigra pars compacta (SNc) and the loss of tyrosine hydroxylase were detected in PD mouse models and the mobility of mouse models was assessed as well. The targeting relationship between miR-132-3p and GLRX was confirmed by RNA immunoprecipitation (RIP) and dual luciferase reporter gene assay. Elevated expression of miR-132-3p and decreased expression of...

Down Syndrome (DS) in humans is caused by trisomy of chromosome 21 and is marked by prominent difficulties in learning and memory. Decades of research have demonstrated that the hippocampus is a key structure in learning and memory, and recent work with mouse models of DS has suggested differences in hippocampal activity that may be the substrate of these differences. One of the primary functional differences in DS is thought to be an excess of GABAergic innervation from Medial Septum (MS) to the hippocampus. In these experiments, we probe in detail the activity of region CA1 of the hippocampus using in vivo electrophysiology in male Ts65Dn mice, in comparison to their male non-trisomic 2N littermates. We find the spatial properties of place cells in CA1 are normal in Ts65Dn animals. However we find that the phasic relationship of both CA1 place cells and gamma rhythms to theta rhythm in the hippocampus are profoundly altered in these mice. Since the phasic organisation of place cell activity and gamma osc...

The neurophysiological processes reflecting body illusions such as the rubber hand remain debated. Previous studies investigating the neural responses evoked by the illusion-inducing stimulation have provided diverging reports as to when these responses reflect the illusory state of the artificial limb becoming embodied. One reason for these diverging reports may be that different studies contrasted different experimental conditions to isolate potential correlates of the illusion, but individual contrasts may reflect multiple facets of the adopted experimental paradigm and not just the illusory state. To resolve these controversies, we recorded EEG responses in human participants and combined multivariate (cross-)classification with multiple Illusion and non-Illusion conditions. These conditions were designed to probe for markers of the illusory state that generalize across the spatial arrangements of limbs or the specific nature of the control object (a rubber hand or participant’s real hand), hence which...

Information transfer and integration in the brain occurs at chemical synapses and is mediated by the fusion of synaptic vesicles filled with neurotransmitter. Synaptic vesicle dynamic spatial organization regulates synaptic transmission as well as synaptic plasticity. Because of their small size, synaptic vesicles require electron microscopy for their imaging, and their analysis is conducted manually. The manual annotation and segmentation of the hundreds to thousands of synaptic vesicles, is highly time consuming and limits the throughput of data collection. To overcome this limitation, we built an algorithm, mainly relying on convolutional neural networks, capable of automatically detecting and localizing synaptic vesicles in electron micrographs. The algorithm was trained on murine synapses but we show that it works well on synapses from different species, ranging from zebrafish to human, and from different preparations. As output, we provide the vesicles count and coordinates, the nearest neighbor dist...

The architecture of the efferent auditory system enables prioritization of strongly overlapping spatiotemporal cochlear activation patterns elicited by relevant and irrelevant inputs. So far, attempts at finding such attentional modulations of cochlear activity delivered indirect insights in humans or required direct recordings in animals. The extent to which spiral ganglion cells forming the human auditory nerve are sensitive to selective attention remains largely unknown. We investigated this question by testing the effects of attending to either the auditory or visual modality in human cochlear implant (CI) users (3 female, 13 male). Auditory nerve activity was directly recorded with standard CIs during a silent (anticipatory) cue-target interval. When attending the upcoming auditory input, ongoing auditory nerve activity within the theta range (5-8 Hz) was enhanced. Crucially, using the broadband signal (4-25 Hz), a classifier was even able to decode the attended modality from single-trial data. Follow...

Strong inhibitory synaptic gating of dentate gyrus granule cells (GCs), attributed largely to fast-spiking parvalbumin interneurons (PV-INs), is essential to maintain sparse network activity needed for dentate dependent behaviors. However, the contribution of PV-INs to basal and input driven sustained synaptic inhibition in GCs and semilunar granule cells (SGCs), a sparse morphologically distinct dentate projection neuron subtype are currently unknown. In studies conducted in hippocampal slices from mice, we find that although basal inhibitory postsynaptic currents (IPSCs) are more frequent in SGCs and optical activation of PV-INs elicited IPSCs in both GCs and SGCs, optical suppression of PV-INs failed to reduce IPSC frequency in either cell type. Amplitude and kinetics of IPSCs evoked by perforant path activation were not different between GCs and SGCs. However, the robust increase in sustained polysynaptic IPSCs elicited by paired afferent stimulation was lower in SGCs than in simultaneously recorded GC...

The dorsal raphe nucleus (DRN) contains the largest population of serotonin (5-HT) neurons in the central nervous system. 5-HT, synthesized via tryptophan hydroxylase 2 (Tph2), is a widely functioning neuromodulator implicated in fear learning. Here, we sought to investigate whether DRN 5-HT is necessary to reduce fear via negative prediction error (–PE). Using male and female TPH2-cre rats, DRNtph2+ cells were selectively deleted via cre-caspase (rAAV5-Flex-taCasp3-TEVp) in experiment 1. Rats then underwent fear discrimination during which three cues were associated with unique foot shock probabilities: safety p  = 0.00, uncertainty p  = 0.375, and danger p  = 1.00. Rats then received selective extinction to the uncertainty cue, a behavioral manipulation designed to probe –PE. Deleting DRNtph2+ cells had no impact on initial discrimination but slowed selective extinction. In experiment 2, we used a within-subjects optogenetic inhibition design to causally implicate DRNtph2+ cells in prediction error signa...

The neuropeptide oxytocin (Oxt) plays important roles in modulating social behaviors. Oxt receptor (Oxtr) is abundantly expressed in the brain and its relationship to socio-behavioral controls has been extensively studied using mouse brains. Several genetic tools to visualize and/or manipulate Oxtr-expressing cells, such as fluorescent reporters and Cre recombinase drivers, have been generated by ES-cell based gene targeting or bacterial artificial chromosome (BAC) transgenesis. However, these mouse lines displayed some differences in their Oxtr expression profiles probably because of the complex context and integrity of their genomic configurations in each line. Here, we apply our sophisticated genome-editing techniques to the Oxtr locus, systematically generating a series of knock-in mouse lines, in which its endogenous transcriptional regulations are intactly preserved and evaluate their expression profiles to ensure the reliability of our new tools. We employ the epitope tagging strategy, with which C-...

In the article, “Resting State BOLD Variability of the Posterior Medial Temporal Lobe Correlates with Cognitive Performance in Older Adults with and without Risk for Cognitive Decline,” by Tyler J. Good, Joshua Villafuerte, Jennifer D. Ryan, Cheryl L. Grady, and Morgan D. Barense, which published online on March 19, 2020, Figure 3 B appeared incorrectly. The values for “3. Memory” …