Biology subjects

Vandael, D.

Publications and source records attributed to Vandael, D..

6 recordsLinked to original sources

bioRxiv2025

Combinatorial Cell-Adhesion and Activity Codes Instruct Cortical Modality Identity

The emergence of functional sensory modalities requires precise cortical arealization and appropriate thalamocortical targeting. Although early morphogen gradients set broad cortical territories, the mechanisms that specify sensory identity and guide modality-specific thalamocortical targeting remain unknown. Here, we identify an embryonic set of activity-independent cortical "protogenes", prominently enriched for cell-adhesion molecules, that are differentially expressed between primary somatosensory (S1) and visual (V1) cortices prior to thalamic innervation. These adhesion programs are selectively localized to layer 4, the main thalamo-recipient layer, and strikingly mirror the adhesion profiles of their corresponding thalamic nuclei, suggesting partner recognition. Disrupting thalamic activity alters modality-specific spontaneous cortical dynamics and the postnatal expression of another set of modality-specific genes, indicating a modulatory role for thalamic activity in cortical identity. These findings support a two-step model in which cortical identity is primed by adhesion codes driving modality-specific thalamocortical targeting, and later refined by patterned thalamic activity to establish functional cortical modalities.

neuroscience↗

bioRxiv2024

Prenatal tuning of thalamic spontaneous activity patterns regulates somatosensory map resolution

Precise mapping of peripheral inputs onto cortical areas is required for appropriate sensory processing. In the mouse primary somatosensory cortex, mystacial whiskers are represented in large barrels, while upper lip whiskers are in smaller, less defined barrels. Barrel size and definition of these two functionally distinct barrel maps are believed to be determined by the type of whisker input and peripheral receptor density. However, spontaneous activity and transcriptional programs at prenatal developmental stages can influence somatosensory map development independently of sensory experience. Thus, the mechanisms defining distinct barrel field territories, including their size and definition, remain poorly understood. Here, we show that prenatal ablation of mystacial whiskers remap somatosensory cortical territories resulting in enhancement of the functional and anatomical definition of upper lip whisker barrels. These changes do not result from alterations in receptor type but rather stem from thalamic upper lip input-receiving neurons adopting a mystacial-like transcriptional profile. Our results unveil a regulated prenatal mechanism within the thalamus that maps available somatosensory input to ensure sufficient cortical barrel size and functional spatial resolution for sensory processing, irrespective of peripheral receptor type and density.

neuroscience↗

bioRxiv2021

Corticotropin-Releasing Factor Induces Functional And Structural Synaptic Remodelling In Acute Stress

Biological responses to internal and external stress factors involve highly conserved mechanisms, using a tightly coordinated interplay of many factors. Corticotropin-releasing factor (CRF) plays a central role in organizing these lifesaving physiological responses to stress. We show that CRF rapidly and reversibly changes Schaffer Collateral input into hippocampal CA1 pyramidal cells (PC), by modulating both functional and structural aspects of these synapses. Host exposure to acute stress, in vivo CRF injection, and ex vivo CRF application all result in fast de novo formation and remodeling of existing dendritic spines. Functionally, CRF leads to a rapid increase in synaptic strength of Schaffer collateral input into CA1 neurons, e.g. increase in spontaneous neurotransmitter release, paired-pulse facilitation and repetitive excitability and improves long-term synaptic plasticity: LTP and LTD. In line with the changes in synaptic function, CRF increases the number of presynaptic vesicles, induces redistribution of vesicles towards the active zone increases active zone size, and improves the alignment of the pre- and post-synaptic compartments. Together, CRF rapidly enhances synaptic communication in the hippocampus, potentially playing a crucial role in the enhanced memory consolidation in acute stress.

neuroscience↗

bioRxiv2020

Transsynaptic modulation of presynaptic short-term plasticity induction in hippocampal mossy fiber synapses

The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit of the hippocampus. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons for induction. Thus, mossy fiber PTP appears to lack cooperativity and associativity that characterize other forms of plasticity. To directly test these predictions, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating parallel but non-overlapping mossy fiber bouton (MFB) inputs converging onto single CA3 neurons, we confirmed that PTP was inputspecific and non-cooperative. Unexpectedly, mossy fiber PTP showed anti-associative induction properties. Mossy fiber excitatory postsynaptic currents (EPSCs) showed only minimal PTP after combined pre- and postsynaptic high-frequency stimulation (HFS) with intact postsynaptic Ca2+ signaling (0.1 mM EGTA), but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP was rescued by blocking Ca2+ entry via voltage-gated R-type and to a smaller extent L-type Ca2+channels. PTP was also recovered by extracellular application of group II metabotropic glutamate receptor (mGluR) antagonists and vacuolar-type (v-type) H+-ATPase inhibitors, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP induction may increase the computational power of mossy fiber synapses, and implement a break on hippocampal mossy fiber detonation.

neuroscience↗

bioRxiv2020

MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo

To understand the mechanisms of information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and the interrelation between these two forms of activity in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in awake, behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events. Here, we developed a new method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. First, experts were asked to manually score short epochs of data. Second, the algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Third, scored and unscored data were processed with the optimal filter, and events were detected as peaks above threshold. Finally, the area under the curve (AUC) of the receiver operating characteristics (ROC) curve was used to quantify accuracy and efficiency of detection. Additionally, cross-validation was performed to exclude overfitting of the scored data, a potential concern with machine-learning approaches. We then challenged the new detection method with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. When benchmarked using a (1-AUC)-1 metric, MOD outperformed previous methods (template-fit and deconvolution) by a factor of up to 3. Thus, MOD may become an important tool for large-scale analysis of synaptic activity in vivo and in vitro. HighlightsO_LIA new method for detection of synaptic events, termed MOD, is described C_LIO_LIThe method combines the concepts of supervised machine learning and optimal filtering C_LIO_LIThe method is useful for analysis of both in vitro and in vivo data sets C_LIO_LIMOD outperforms previously published methods for synaptic event detection by a factor of up to 3 C_LI

neuroscience↗

bioRxiv2020

GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals

The connection from medial habenula (MHb) to interpeduncular nucleus is critical for aversion- and addiction-related behaviors. This pathway is unique in selective expression of R-type voltage-gated Ca2+ channels (Cav2.3) in its terminals, and robust potentiation of release via presynaptic GABAB receptors (GBRs). To understand the mechanism underlying this peculiar GBR effect, we examined the presynaptic localization and function of Cav2.3, GBR, and its auxiliary subunits, K+-channel tetramerization domain-containing (KCTD) proteins. We found selective co-expression of KCTD12b and Cav2.3 at the presynaptic active zone. GBR-mediated potentiation remained intact in KCTD12b KO mice but lasted significantly shorter. This impairment was associated with increased release and an insertion of KCTD8 into the active zone. In heterologous cells, we found direct binding of KCTD8 and KCTD12b to Cav2.3, and potentiation of Cav2.3 currents by KCTD8. The unexpected interaction of Cav2.3 with KCTDs therefore provides a means to scale synaptic strength independent of GBR activation.

neuroscience↗