A cortical circuit for voluntary laryngeal control: Implications for the evolution language

AbstractHumans are endowed with an exceptional ability for detecting faces, a competence that in adults is supported by a set of face-specific cortical patches. Human newborns already shortly after birth preferentially orient to faces even when they are presented in the form of highly schematic geometrical patterns, over perceptually equivalent non-face-like stimuli. The neural substrates underlying this early preference are still largely unexplored. Is the adult face-specific cortical circuit already active at birth, or does its specialization develop slowly as a function of experience and/or maturation? We measured EEG responses in 1-4 days old awake, attentive human newborns to schematic face-like patterns and non-face-like control stimuli, visually presented with a slow oscillatory “peekaboo” dynamics (0.8 Hz) in a frequency-tagging design. Despite the limited duration of newborns’ attention, reliable frequency-tagged responses could be estimated for each stimulus from the peak of the EEG power spectrum at the stimulation frequency. Upright face-like stimuli elicited a significantly stronger frequency-tagged response than inverted face-like controls in a large set of electrodes. Source reconstruction of the underlying cortical activity revealed the recruitment of a partially right-lateralized network comprising lateral occipito-temporal and medial parietal areas largely overlapping with the adult face-processing circuit. This result suggests that the cortical route specialized in face processing is already functional at birth.Significance statementNewborns show a remarkable ability to detect faces even minutes after birth, an ecologically fundamental skill that is instrumental for interacting with their conspecifics. What are the neural bases of this expertise? Using EEG and a slow oscillatory visual stimulation, we identified a reliable response specific to face-like patterns in newborns, which underlying cortical sources largely overlap with the adult face-specific cortical circuit. This suggests that the development of face perception in infants might rely on an early cortical route specialized in face processing already shortly after birth.

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Cortical circuit alterations precede disease onset in Huntington’s disease mice

10.1101/391771 ◽

2018 ◽

Author(s):

Johanna Neuner ◽

Elena Katharina Schulz-Trieglaff ◽

Sara Gutiérrez-Ángel ◽

Fabian Hosp ◽

Matthias Mann ◽

...

Keyword(s):

Motor Cortex ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Primary Motor Cortex ◽

Disease Onset ◽

Single Neurons ◽

Two Photon ◽

Layer 2 ◽

Cortical Circuit

AbstractHuntington’s disease (HD) is a devastating hereditary movement disorder, characterized by degeneration of neurons in the striatum and cortex. Studies in human patients and mouse HD models suggest that disturbances of neuronal function in the neocortex play an important role in the disease onset and progression. However, the precise nature and time course of cortical alterations in HD have remained elusive. Here, we use chronicin vivotwo-photon calcium imaging to monitor the activity of single neurons in layer 2/3 of the primary motor cortex in awake, behaving R6/2 transgenic HD mice and wildtype littermates. R6/2 mice show age-dependent changes in neuronal activity with a clear increase in activity at the age of 8.5 weeks, preceding the onset of motor and neurological symptoms. Furthermore, quantitative proteomics demonstrate a pronounced downregulation of synaptic proteins in the cortex, and histological analyses in R6/2 mice and HD patient samples reveal reduced inputs from parvalbumin-positive interneurons onto layer 2/3 pyramidal cells. Thus, our study provides a time-resolved description as well as mechanistic details of cortical circuit dysfunction in HD.Significance statementFuntional alterations in the cortex are believed to play an important role in the pathogenesis of Huntington’s disease (HD). However, studies monitoring cortical activity in HD modelsin vivoat a single-cell resultion are still lacking. We have used chronic two-photon imaging to investigate changes in the activity of single neurons in the primary motor cortex of awake presymptomatic HD mice. We show that neuronal activity increases before the mice develop disease symptoms. Our histological analyses in mice and in human HD autopsy cases furthermore demonstrate a loss inhibitory synaptic terminals from parvalbimun-positive interneurons, revealing a potential mechanism of cortical circuit impairment in HD.

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Reconstruction and visualization of large-scale volumetric models of neocortical circuits for physically-plausible in silico optical studies

10.1101/164483 ◽

2017 ◽

Author(s):

Marwan Abdellah ◽

Juan Hernando ◽

Nicolas Antille ◽

Stefan Eilemann ◽

Henry Markram ◽

...

Keyword(s):

In Silico ◽

Large Scale ◽

Circuit Model ◽

Optical Studies ◽

Domain Experts ◽

Multi Stage ◽

Volumetric Models ◽

Imaging Experiment ◽

Cortical Circuit ◽

Tissue Models

AbstractBackground We present a software workflow capable of building large scale, highly detailed and realistic volumetric models of neocortical circuits from the morphological skeletons of their digitally reconstructed neurons. The limitations of the existing approaches for creating those models are explained, and then, a multi-stage pipeline is discussed to overcome those limitations. Starting from the neuronal morphologies, we create smooth piecewise watertight polygonal models that can be efficiently utilized to synthesize continuous and plausible volumetric models of the neurons with solid voxelization. The somata of the neurons are reconstructed on a physically-plausible basis relying on the physics engine in Blender.Results Our pipeline is applied to create 55 exemplar neurons representing the various morphological types that are reconstructed from the somatsensory cortex of a juvenile rat. The pipeline is then used to reconstruct a volumetric slice of a cortical circuit model that contains ∼210,000 neurons. The applicability of our pipeline to create highly realistic volumetric models of neocortical circuits is demonstrated with an in silico imaging experiment that simulates tissue visualization with brightfield microscopy. The results were evaluated with a group of domain experts to address their demands and also to extend the workflow based on their feedback.Conclusion A systematic workflow is presented to create large scale synthetic tissue models of the neocortical circuitry. This workflow is fundamental to enlarge the scale of in silico neuroscientific optical experiments from several tens of cubic micrometers to a few cubic millimeters.

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Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology

Journal of Neuroinflammation ◽

10.1186/s12974-021-02260-6 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Amira Ben Afia ◽

Èlia Vila ◽

Karina S. MacDowell ◽

Aida Ormazabal ◽

Juan C. Leza ◽

...

Keyword(s):

Prefrontal Cortex ◽

High Performance ◽

Interaction Analysis ◽

Kynurenine Pathway ◽

Psychotic Symptoms ◽

Post Mortem ◽

Control Subjects ◽

Network Interaction ◽

Hydroxyindoleacetic Acid ◽

Cortical Circuit

Abstract Background The cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA). Methods This work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by high-performance liquid chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored. Results In the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzyme expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolite content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC. Conclusions Thus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.

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