VGLUT2 functions as a differentia marker for hippocampal output neurons

The subiculum is the gatekeeper between the hippocampus and cortical areas. Yet, the lack of a pyramidal cell-specific marker gene has made the analysis of the subicular area very difficult. Here we report that the vesicular-glutamate transporter 2 (VGLUT2) functions as a specific marker gene for subicular burst-firing neurons, and demonstrate that VGLUT2-Cre mice allow for Channelrhodopsin-2 (ChR2)-assisted connectivity analysis

VGLUT2 functions as a differential marker for hippocampal output neurons

The subiculum is the gatekeeper between the hippocampus and cortical areas. Yet, the lack of a pyramidal cell-specific marker gene has made the analysis of the subicular area very difficult. Here we report that the vesicular-glutamate transporter 2 (VGLUT2) functions as a specific marker gene for subicular burst-firing neurons, and demonstrate that VGLUT2-Cre mice allow for Channelrhodopsin-2 (ChR2)-assisted connectivity analysis

Process-based framework for precise neuromodulation

Functional MRI neurofeedback (NF) allows humans to self-modulate neural patterns in specific brain areas. This technique is regarded as a promising tool to translate neuroscientific knowledge into brain-guided psychiatric interventions. However, its clinical implementation is restricted by unstandardized methodological practices, by clinical definitions that are poorly grounded in neurobiology, and by lack of a unifying framework that dictates experimental choices. Here we put forward a new framework, termed ‘process-based NF’, which endorses a process-oriented characterization of mental dysfunctions to form precise and effective psychiatric treatments. This framework relies on targeting specific dysfunctional mental processes by modifying their underlying neural mechanisms and on applying process-specific contextual feedback interfaces. Finally, process-based NF offers designs and a control condition that address the methodological shortcomings of current approaches, thus paving the way for a precise and personalized neuromodulation

VGLUT2 Functions as a Differential Marker for Hippocampal Output Neurons

The subiculum is the gatekeeper between the hippocampus and cortical areas. Yet, the lack of a pyramidal cell-specific marker gene has made the analysis of the subicular area very difficult. Here we report that the vesicular-glutamate transporter 2 (VGLUT2) functions as a specific marker gene for subicular burst-firing neurons, and demonstrate that VGLUT2-Cre mice allow for Channelrhodopsin-2 (ChR2)-assisted connectivity analysis

Propagation von hippokampalen Ripples in den Neokortex über die subikulo-retrospinale Verbindung

Sharp wave ripple (SPW-R) events are brief high frequency oscillations observed throughout the hippocampal network during slow-wave sleep and quiet wakefulness. This transient synchronous activity provides the physiological scaffold for the compressed replay of awake sequences, and accumulating data support their crucial role in memory consolidation. The wide range of cortical areas that are strongly depolarized during SPW-Rs, as well as the observed coordinated reactivation of hippocampal and neocortical neural ensembles during slow wave sleep, both support the idea that memory consolidation involves the transfer of processed hippocampal information for long-term storage in distributed cortical networks. However, the majority of these cortical areas do not receive direct hippocampal projections and little is known about the routes taken by neural activity that can support this process. A prominent, yet under-investigated area that may act as a hippocampo-cortical relay is the retrosplenial cortex. Using silicon probe recordings in awake head-fixed mice, we report here the coordinated interplay of retrosplenial and hippocampal activity during SPW-Rs and the existence of SPW-Rs analogues in the retrosplenial cortex. We show that these interactions are topographically organized and layer specific. Using large-coverage high-density recordings, we demonstrate the existence of multiple subclasses of SPW-Rs and show that retrosplenial neurons are tuned to specific constellations of hippocampal output during SPW-Rs. Finally, we show that hippocampal output to the retrosplenial cortex is mediated by a genetically defined subpopulation of subicular bursty neurons. We demonstrate that optogenetically stimulating these vesicular glutamate transporter 2-expressing neurons is sufficient to evoke cortical ripple responses in superficial retrosplenial cortex, while optogenetic inhibition significantly reduces such responses. These results yield a mechanistic understanding of the neural substrate underlying hippocampal-cortical interactions during the awake resting state, and provide insights into how the offline transfer of previously stored information from the hippocampus to the cortex may be coordinated

A comparison of attention-deficit/hyperactivity disorder with autism spectrum disorder on cognitive, neural, and emotional estimates: a systematic review

Background: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two neurodevelopmental disorders that share common symptoms and frequently co-occur. We performed a systematic review of studies examining three main domains in ADHD vs ASD; executive functions, brain structures and functions, and emotional skills, in an effort to better understand their co-occurrence. Methods: As ADHD and ASD frequently co-occur, we chose to focus on the relevant articles comparing ADHD (with no ASD) and ASD (with no ADHD) populations using appropriate measures. A systematic literature search was conducted using six electronic databases, up to May 18, 2022. Results: A total of 19 articles were included. No significant differences were found in executive functioning between ADHD and ASD. For emotional skills, results were inconclusive, with greater theory of mind (ToM) and empathy skills in ADHD relative to ASD, but no significant differences in emotion recognition. Regarding brain structure and functions, there were inconsistent findings, with some studies reporting weaker brain connectivity in ASD, and reduced gray and white matter volumes in ADHD, while others reported no significant differences. Conclusions: Our review suggests a lack of studies directly examining ASD compared with ADHD. The existing literature does not suggest a unique association of either ASD/ADHD with executive dysfunction, emotional skills deficits, or brain structure/function abnormalities. Consequently, further research is necessary to develop a more comprehensive understanding of the overlaps and differences between these disorders and to address the existing gaps in knowledge

Molecular determinants of proton selectivity and gating in the red-light activated channelrhodopsin Chrimson

Abstract Channelrhodopsins are light-gated ion channels of green algae used for the precise temporal and spatial control of transmembrane ion fluxes. The channelrhodopsin Chrimson from Chlamydomonas noctigama allows unprecedented deep tissue penetration due to peak absorption at 590 nm. We demonstrate by electrophysiological recordings and imaging techniques that Chrimson is highly proton selective causing intracellular acidification in HEK cells that is responsible for slow photocurrent decline during prolonged illumination. We localized molecular determinants of both high proton selectivity and red light activation to the extracellular pore. Whereas exchange of Glu143 only drops proton conductance and generates an operational Na-channel with 590 nm activation, exchange of Glu139 in addition increased the open state lifetime and shifted the absorption hypsochromic by 70 nm. In conjunction with Glu300 in the center and Glu124 and Glu125 at the intracellular end of the pore, Glu139 contributes to a delocalized activation gate and stabilizes by long-range interaction counterion configuration involving protonation of Glu165 that we identified as a key determinant of the large opsin shift in Chrimson

Species-specific differences in synaptic transmission and plasticity

Synaptic transmission and plasticity in the hippocampus are integral factors in learning and memory. While there has been intense investigation of these critical mechanisms in the brain of rodents, we lack a broader understanding of the generality of these processes across species. We investigated one of the smallest animals with conserved hippocampal macroanatomy—the Etruscan shrew, and found that while synaptic properties and plasticity in CA1 Schaffer collateral synapses were similar to mice, CA3 mossy fiber synapses showed striking differences in synaptic plasticity between shrews and mice. Shrew mossy fibers have lower long term plasticity compared to mice. Short term plasticity and the expression of a key protein involved in it, synaptotagmin 7 were also markedly lower at the mossy fibers in shrews than in mice. We also observed similar lower expression of synaptotagmin 7 in the mossy fibers of bats that are evolutionarily closer to shrews than mice. Species specific differences in synaptic plasticity and the key molecules regulating it, highlight the evolutionary divergence of neuronal circuit functions