Postsynaptic scaffolding proteins function as central organization hubs, ensuring the synaptic localization of neurotransmitter receptors, trans-synaptic adhesion proteins, and signaling molecules. Gephyrin is the major postsynaptic scaffolding protein at glycinergic and a subset of GABAergic inhibitory synapses. In contrast to cells outside the CNS, where one gephyrin isoform is predominantly expressed, neurons express different splice variants. In this study, we characterized the expression and scaffolding of neuronal gephyrin isoforms differing in the inclusion of the C4 cassettes located in the central C-domain. In hippocampal and cortical neuronal populations, gephyrin P1, lacking additional cassettes, is the most abundantly expressed isoform. In addition, alternative splicing generated isoforms carrying predominantly C4a, and minor amounts of C4c or C4d cassettes. We detected no striking difference in C4 isoform expression between different neuron types and a single neuron can likely express all C4 i...

The tuning properties of neurons in the visual system can be contextually modulated by the statistics of the area surrounding their receptive field, particularly when the surround contains natural features. However, stimuli presented in specific egocentric locations may have greater behavioural relevance, raising the possibility that the extent of contextual modulation may vary with position in visual space. To explore this possibility we utilised the small size and optical transparency of the larval zebrafish to describe the form and spatial arrangement of contextually modulated cells throughout an entire tectal hemisphere. We found that the spatial tuning of tectal neurons to a prey-like stimulus sharpens when the stimulus is presented against a background with the statistics of complex natural scenes, relative to a featureless background. These neurons are confined to a spatially restricted region of the tectum and have receptive fields centred within a region of visual space in which the presence of pr...

Objective: To use machine learning to predict AIS scores for newly injured SCI patients at hospital discharge time from hospital admission data. Additionally, to analyze the best model for feature importance in order to validate the criticality of AIS score and highlight relevant demographic details. Design: Data used for training machine learning models was from the NSCISC database of United States SCI patient details. 18 real features were used from 417 provided ones, which mapped to 53 machine learning features after processing. 8 models were tuned on the dataset to predict AIS scores and Shapely analysis was performed to extract the most important of the 53 features. Participants: Patients within the NSCISC database who sustained injuries between 1972 and 2016 after data cleaning (n = 20,790). Outcome Measures: Test set multi-class and aggregated Shapely score magnitudes. Results: Ridge Classifier was the best performer with 73.6% test set accuracy. AIS scores and neurologic category at admission t...

Retinal ganglion cell (RGC) axons comprise the optic nerve and carry information to the dorsolateral geniculate nucleus (dLGN) which is then relayed to the cortex for conscious vision. Glaucoma is a blinding neurodegenerative disease that commonly results from intraocular pressure (IOP)-associated injury leading to RGC axonal pathology, disruption of RGC outputs to the brain, and eventual apoptotic loss of RGC somata. The consequences of elevated IOP and glaucomatous pathology on RGC signaling to the dLGN are largely unknown yet are likely to contribute to vision loss. Here, we used anatomical and physiological approaches to study the structure and function of retinogeniculate (RG) synapses in male and female DBA/2J (D2) mice with inherited glaucoma before and after IOP elevation. D2 mice showed progressive loss of anterograde optic tract transport to the dLGN and vGlut2 labeling of RGC axon terminals while patch-clamp measurements of RG synaptic function showed that synaptic transmission was reduced in 9 ...

Environmental enrichment (EE) is beneficial for brain development and function, but our understanding of its capacity to drive circuit repair, the underlying mechanisms, and how this might vary with age remains limited. Ten-m3 knockout (KO) mice exhibit a dramatic and stereotyped mistargeting of ipsilateral retinal inputs to the thalamus, resulting in visual deficits. We have recently shown a previously unexpected capacity for EE during early postnatal life (from birth for 6 weeks) to drive the partial elimination of miswired axonal projections, along with a recovery of visually mediated behaviour, but the timeline of this repair was unclear. Here, we reveal that with just 3.5 weeks of EE from birth, Ten-m3 KOs exhibit a partial behavioural rescue, accompanied by pruning of the most profoundly miswired retinogeniculate terminals. Analysis suggests that the pruning is underway at this time point, providing an ideal opportunity to probe potential mechanisms. With the shorter EE-period, we found a localised i...

Sleep facilitates memory storage and even brief periods of sleep loss lead to impairments in memory, particularly memories that are hippocampus dependent. In previous studies, we have shown that the deficit in memory seen after sleep loss is accompanied by deficits in synaptic plasticity. Our previous work has also found that sleep deprivation is associated with reduced levels of cyclic adenosine monophosphate (cAMP) in the hippocampus, and that the reduction of cAMP mediates the diminished memory observed in sleep-deprived animals. Based on these findings, we hypothesized that cAMP acts as a mediator for not only the cognitive deficits caused by sleep deprivation, but also the observed deficits in synaptic plasticity. In this study, we expressed the heterologous Drosophila melanogaster Gαs-protein coupled octopamine receptor (DmOctβ1R) in mouse hippocampal neurons. This receptor is selectively activated by the systemically injected ligand (octopamine), thus allowing us to increase cAMP levels in hippocamp...

Understanding how the brain functions differently as one learns to read may shed light on the controversial nature of the reading ability of human being. Logographic writing system such as Chinese has been found to rely on specialized neural substrates beyond the reading network of alphabetic languages. The ability to read in Chinese has also been proposed to rely on writing skills. However, it was unclear whether the learning-related alteration of neural responses was language-specific or resulted from the more reliance on writing practice during acquisition. This study investigated whether the emergence of typical logographic-specific regions relied on learning by writing. We taught proficient alphabetic language readers Chinese characters and used pre- and post-tests to identify changes in two critical stages of reading, namely orthographic processing and orthographic-to-phonological mapping. Two typical left hemispheric areas for logographic reading showed increased responses to characters in the brain...

Avoiding potentially harmful, and consuming safe food is crucial for the survival of living organisms. However, the perceived valence of sensory information can change following conflicting experiences. Pleasurability and aversiveness are two crucial parameters defining the perceived valence of a taste and can be impacted by novelty. Importantly, the ability of a given taste to serve as the conditioned stimulus (CS) in conditioned taste aversion (CTA), is dependent on its valence. Activity in anterior insula (aIC) layer IV-VI pyramidal neurons projecting to the basolateral amygdala (BLA) is correlated with, and necessary for CTA learning and retrieval, as well as the expression of neophobia towards novel tastants, but not learning taste familiarity. Yet, the cellular mechanisms underlying the updating of taste valence representation in this specific pathway are poorly understood. Here, using retrograde viral tracing and whole -cell patch-clamp electrophysiology in trained mice, we demonstrate that the intr...

Sign- versus goal-tracking in rats indicate vulnerability and resistance, respectively, to Pavlovian cue-evoked addictive drug taking and relapse. Here we tested hypotheses predicting that the opponent cognitive-behavioral styles indexed by sign- versus goal tracking include variations in attentional performance which differentially depend on basal forebrain projection systems. Pavlovian Conditioned Approach (PCA) testing was used to identify male and female sign-trackers (STs) and goal-trackers (GTs), as well as rats with an intermediate phenotype (INTs). Upon reaching asymptotic performance in an operant task requiring the detection of visual signals (hits) as well as the reporting of signal absence for 40 min per session, GTs scored more hits than STs, and hit rates across all phenotypes correlated with PCA scores. STs missed relatively more signals than GTs specifically during the last 15 min of a session. Chemogenetic inhibition of the basal forebrain decreased hit rates in GTs but was without effect ...

Navigating through an environment requires knowledge about one’s direction of self-motion (heading) and traveled distance. Behavioral studies showed that human participants can actively reproduce a previously observed travel distance purely based on visual information. Here, we employed EEG to investigate the underlying neural processes. We measured in human observers event-related potentials (ERPs) during visually simulated straight-forward self-motion across a ground plane. The participants’ task was to reproduce (active condition) double the distance of a previously seen self-displacement (passive condition) using a gamepad. We recorded the trajectories of self-motion during the active condition and played it back to the participants in a third set of trials (replay condition). We analyzed EEG activity separately for four electrode clusters: frontal (F), central (C), parietal (P), and occipital (O). When aligned to self-motion on- or offset, response modulation of the ERPs was stronger, and several ERP-...