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Gracias, A.

Publications and source records attributed to Gracias, A..

4 recordsLinked to original sources

Spatial predictive coding in visual cortical neurons

Predictive coding is a theoretical framework that can explain how animals build internal models of their sensory environments by predicting sensory inputs. Predictive coding may capture either spatial or temporal relationships between sensory objects. While the original theory by Rao and Ballard, 1999 described spatial predictive coding, much of the recent experimental data has been interpreted as evidence for temporal predictive coding. Here we directly tested whether the "mismatch" neural responses in sensory cortex are due to a spatial or a temporal internal model. We adopted two common paradigms to study predictive coding: one based on virtual-reality and one based on static images. After training mice with repeated visual stimulation for several days, we performed multiple manipulations, including: 1) we introduced a novel stimulus, 2) we replaced a stimulus with a novel gray wall, 3) we duplicated a trained stimulus, or 4) we altered the order of the stimuli. The first two manipulations induced a substantial mismatch response in neural populations of up to 20,000 neurons recorded across primary and higher-order visual cortex, while the third and fourth ones did not. Thus, a mismatch response only occurred if a new spatial - not temporal - pattern was introduced.

neuroscience↗

A critical initialization for biological neural networks

Artificial neural networks learn faster if they are initialized well. Good initializations can generate high-dimensional macroscopic dynamics with long timescales. It is not known if biological neural networks have similar properties. Here we show that the eigenvalue spectrum and dynamical properties of large-scale neural recordings in mice (two-photon and electrophysiology) are similar to those produced by linear dynamics governed by a random symmetric matrix that is critically normalized. An exception was hippocampal area CA1: population activity in this area resembled an efficient, uncorrelated neural code, which may be optimized for information storage capacity. Global emergent activity modes persisted in simulations with sparse, clustered or spatial connectivity. We hypothesize that the spontaneous neural activity reflects a critical initialization of whole-brain neural circuits that is optimized for learning time-dependent tasks.

neuroscience↗

Chronic alcohol induces subcircuit-specific striatonigral plasticity shifting action control to the sensorimotor striatum

While cortico-striatal circuit deficits contribute to Alcohol Use Disorder, the impact of alcohol on synaptic function in the basal ganglia output, the substantia nigra pars reticulata (SNr), remains unclear. Here, we found that the inputs from the dorsomedial (DMS) and dorsolateral striatum (DLS) differ in their presynaptic properties and target molecularly distinct subpopulations of SNr neurons. We also discovered that indirect pathway subthalamic (STN) inputs to the medial and lateral SNr have different presynaptic properties and that STN inputs are stronger in the lateral SNr. Chronic alcohol exposure (CIE) potentiated DLS inputs but did not affect the strength and presynaptic release properties of DMS and subthalamic inputs to SNr neurons. Chemogenetic inhibition of DLS direct pathway projection neurons impaired action performance in an operant conditioning task in CIE mice but not control mice. Overall, our work identifies a synaptic mechanism whereby chronic alcohol induces a gain of function for action control in direct pathway neurons in the dorsolateral striatum. TeaserChronic alcohol selectively potentiates DLS synaptic inputs to the SNr, enhancing their role in action control.

neuroscience↗

Live detection of neural stem and glioblastoma cells by an oligothiophene derivative

Here we report a luminescent conjugated oligothiophene (LCO), named p-HTMI, for non-invasive and non-amplified real-time detection of live human patient-derived glioblastoma (GBM) cells and embryonic neural stem cells (NSCs). While p-HTMI stained only a small fraction of other cell types investigated, the mere addition of p-HTMI to the cell culture resulted in efficient detection of NSCs or GBM cells from rodents and humans within minutes. p-HTMI is functionalized with a methylated imidazole moiety resembling the side chain of histidine/histamine, and non-methylated analogues were not functional. p-HTMI were readily able to detect a subpopulation of human cells in vivo in mouse brain sections with tumors developed from orthotopically transplanted patient-derived GBM cells. Cell sorting experiments of human GBM cells demonstrated that p-HTMI labeled the same population as CD271, a proposed marker for stem cell-like cells and rapidly migrating cells in glioblastoma. Our results suggest that the LCO p-HTMI is a versatile tool for immediate and selective detection of subpopulations of neural stem and glioma cells.

bioengineering↗