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Anastasiades, P.

Publications and source records attributed to Anastasiades, P..

3 recordsLinked to original sources

A theory of temporal self-supervised learning in neocortical layers

The neocortex constructs an internal representation of the world, but the underlying circuitry and computational principles remain unclear. Inspired by self-supervised learning algorithms, we introduce a computational theory wherein layer 2/3 (L2/3) learns to predict incoming sensory stimuli by comparing previous sensory inputs, relayed via layer 4, with current thalamic inputs arriving at layer 5 (L5). We demonstrate that our model accurately predicts sensory information in context-dependent temporal tasks, and that its predictions are robust to noisy and occluded sensory input. Additionally, our model generates layer-specific sparsity and latent representations, consistent with experimental observations. Next, using a sensorimotor task, we show that the models L2/3 and L5 prediction errors mirror mismatch responses observed in awake, behaving mice. Finally, through manipulations, we offer testable predictions to unveil the computational roles of various cortical features. In summary, our findings suggest that the multi-layered neocortex empowers the brain with self-supervised predictive learning.

neuroscience↗

Cell type-specific disruption of cortico-striatal circuitry drive repetitive patterns of behaviour in fragile X syndrome model mice

Individuals with fragile X syndrome (FXS) are frequently diagnosed with autism spectrum disorder (ASD), including increased risk for restricted and repetitive behaviours (RRBs). Consistent with observations in humans, FXS model mice display distinct RRBs and hyperactivity that are consistent with dysfunctional cortico-striatal circuits, an area relatively unexplored in FXS. Using a multidisciplinary approach, we dissected the contribution of two populations of striatal medium spiny neurons (SPNs) in the expression of RRBs in FXS model mice. We found that dysregulated protein synthesis at cortico-striatal synapses is a molecular culprit of the synaptic and ASD-associated motor phenotypes displayed by FXS model mice. Cell-type-specific translational profiling of the FXS mouse striatum revealed differentially translated mRNAs, providing critical information concerning potential therapeutic targets. Our findings represent the first evidence of a cell-type specific impact of the loss of FMRP on translation and the sequence of neuronal events in the striatum that drive RRBs in FXS. HighlightsDysregulated striatal protein synthesis underlies altered synaptic plasticity and RRBs displayed by FXS model mice FXS model mice exhibit cell type-specific molecular, morphological, and synaptic changes in the dorsolateral striatum Selective deletion of Fmr1 from dSNPs in mice alters translation and causes repetitive behavior TRAP-Seq indicates that there is altered binding of >120 mRNAs to ribosomes in dSNPs of Fmr1 KO mice G-protein signaling (RGS) 4 translation is significantly reduced in dSPNs in FXS model mice Treatment of FXS model mice with VU0152100, a positive allosteric modulator of the M4 muscarinic receptor that is upstream of RGS4, can reverse RRBs

neuroscience↗

Cell-type specific D1 dopamine receptor modulation of projection neurons and interneurons in the prefrontal cortex

Dopamine modulation in the prefrontal cortex (PFC) mediates diverse effects on neuronal physiology and function, but the expression of dopamine receptors at sub-populations of pyramidal neurons and interneurons remains unresolved. Here, we examine D1 receptor expression and modulation at specific cell types and layers in the mouse prelimbic PFC. We first show that D1 receptors are enriched in pyramidal neurons in both layers 5 and 6, and that these cells project intra-telencephalically, rather than to sub-cortical structures. We then find that D1 receptors are also present in interneurons, and enriched in VIP+ interneurons that co-expresses calretinin, but absent from PV+ and SOM+ interneurons. Finally, we determine that D1 receptors strongly and selectively enhance action potential firing in only a subset of these cortico-cortical neurons and VIP+ interneurons. Our findings define several novel sub-populations of D1+ neurons, highlighting how modulation via D1 receptors can influence both excitatory and disinhibitory micro-circuits in the PFC.

neuroscience↗