Exploring Cortical Interneurons in Substance Use Disorder: From Mechanisms to Therapeutic Perspectives

The Neuroscientist, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Interneurons (INs) play a crucial role in the regulation of neural activity within medial prefrontal cortex (mPFC), brain region critically involved executive functions and behavioral control. In recent preclinical studies, dysregulation INs mPFC has been implicated pathophysiology substance use disorder, characterized by vulnerability to chronic drug use. Here, we explore diversity their connectivity roles addiction. We also discuss how these change over time with exposure. Finally, focus on noninvasive stimulation as therapeutic approach for targeting highlighting its potential restore circuits.

Язык: Английский

---

Ensemble priming via competitive inhibition: local mechanisms of sensory context storage and deviance detection in the neocortical column

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

The process by which neocortical neurons and circuits amplify their response to an unexpected change in stimulus, often referred as deviance detection (DD), has long been thought be the product of specialized cell types and/or routing between mesoscopic brain areas. Here, we explore a different theory, whereby DD emerges from local network-level interactions within column. We propose that deviance-driven neural dynamics can emerge through ensembles have fundamental inhibitory motif: competitive inhibition reciprocally connected under modulation feed-forward selective (dis)inhibition. Using this framework, were able simulate variety phenomena pertaining experimentally observed shifts tuning across neurons, time, stimulus history. Anchoring our approach phenomena, used computation modeling two networks vastly levels biophysical detail test hypotheses on emergent robustness underlying connectivity parameters. With number corollary predictions tested future vivo studies, show ensemble priming via (dis)inhibition acts mechanism for sensory context storage does not require input other areas-a novel theoretical paradigm resolves previously confounding aspects encoding predictive processing neocortex.

Язык: Английский

---

Geometry and dynamics of representations in a precisely balanced memory network related to olfactory cortex

eLife, Год журнала: 2025, Номер 13

Опубликована: Янв. 13, 2025

Biological memory networks are thought to store information by experience-dependent changes in the synaptic connectivity between assemblies of neurons. Recent models suggest that these contain both excitatory and inhibitory neurons (E/I assemblies), resulting co-tuning precise balance excitation inhibition. To understand computational consequences E/I under biologically realistic constraints we built a spiking network model based on experimental data from telencephalic area Dp adult zebrafish, precisely balanced recurrent homologous piriform cortex. We found stabilized firing rate distributions compared with global Unlike classical models, did not show discrete attractor dynamics. Rather, responses learned inputs were locally constrained onto manifolds ‘focused’ activity into neuronal subspaces. The covariance structure supported pattern classification when was retrieved selected subsets. Networks therefore transformed geometry coding space, continuous representations reflected relatedness an individual’s experience. Such enable fast classification, can support continual learning, may provide basis for higher-order learning cognitive computations.

Язык: Английский

---

Experience-dependent reorganization of inhibitory neuron synaptic connectivity

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Organisms continually tune their perceptual systems to the features they encounter in environment 1-3 . We have studied how ongoing experience reorganizes synaptic connectivity of neurons olfactory (piriform) cortex mouse. developed an approach measure vivo , training a deep convolutional network reliably identify monosynaptic connections from spike-time cross-correlograms 4.4 million single-unit pairs. This revealed that excitatory piriform with similar odor tuning are more likely be connected. asked whether enhances this like-to-like but found it was unaffected by exposure. Experience did, however, alter logic interneuron connectivity. Following repeated encounters set odorants, inhibitory responded differentially these stimuli exhibited high degree both incoming and outgoing within cortical network. reorganization depended only on not its pre- or postsynaptic partners. A computational model reorganized predicts increases dimensionality entire network's responses familiar stimuli, thereby enhancing discriminability. confirmed network-level property is present physiological measurements, which showed increased separability evoked versus novel odorants. Thus, simple, non-Hebbian may selectively enhance organism's discrimination environment.

Язык: Английский

---

Uncertainty-modulated prediction errors in cortical microcircuits

Опубликована: Янв. 22, 2025

Understanding the variability of environment is essential to function in everyday life. The brain must hence take uncertainty into account when updating its internal model world. basis for are prediction errors that arise from a difference between current and new sensory experiences. Although error neurons have been identified layer 2/3 diverse areas, how modulates these learning is, however, unclear. Here, we use normative approach derive should modulate postulate represent uncertainty-modulated (UPE). We further hypothesise circuit calculates UPE through subtractive divisive inhibition by different inhibitory cell types. By implementing calculation UPEs microcircuit model, show types can compute means variances stimulus distribution. With local activity-dependent plasticity rules, computations be learned context-dependently, allow upcoming stimuli their Finally, mechanism enables an organism optimise strategy via adaptive rates.

Язык: Английский

---

Efficient coding in biophysically realistic excitatory-inhibitory spiking networks

Опубликована: Янв. 22, 2025

The principle of efficient coding posits that sensory cortical networks are designed to encode maximal information with minimal metabolic cost. Despite the major influence in neuroscience, it has remained unclear whether fundamental empirical properties neural network activity can be explained solely based on this normative principle. Here, we derive structural, coding, and biophysical excitatory-inhibitory recurrent spiking neurons emerge directly from imposing minimizes an instantaneous loss function a time-averaged performance measure enacting coding. We assumed encodes number independent stimulus features varying time scale equal membrane constant excitatory inhibitory neurons. optimal biologically-plausible features, including realistic integrate-and-fire dynamics, spike-triggered adaptation, non-specific external input. connectivity between similar tuning implements feature-specific competition, recently found visual cortex. Networks unstructured cannot reach comparable levels efficiency. ratio vs mean inhibitory-to-inhibitory excitatory-to-inhibitory those networks. solution exhibits balance excitation inhibition. perform even when stimuli vary over multiple scales. Together, these results suggest key biological may accounted for by

Язык: Английский

---

Efficient coding in biophysically realistic excitatory-inhibitory spiking networks

Опубликована: Янв. 30, 2025

The principle of efficient coding posits that sensory cortical networks are designed to encode maximal information with minimal metabolic cost. Despite the major influence in neuroscience, it has remained unclear whether fundamental empirical properties neural network activity can be explained solely based on this normative principle. Here, we derive structural, coding, and biophysical excitatory-inhibitory recurrent spiking neurons emerge directly from imposing minimizes an instantaneous loss function a time-averaged performance measure enacting coding. We assumed encodes number independent stimulus features varying time scale equal membrane constant excitatory inhibitory neurons. optimal biologically-plausible features, including realistic integrate-and-fire dynamics, spike-triggered adaptation, non-specific external input. connectivity between similar tuning implements feature-specific competition, recently found visual cortex. Networks unstructured cannot reach comparable levels efficiency. ratio vs mean inhibitory-to-inhibitory excitatory-to-inhibitory those networks. solution exhibits balance excitation inhibition. perform even when stimuli vary over multiple scales. Together, these results suggest key biological may accounted for by

Язык: Английский

---

A systematic analysis of the joint effects of ganglion cells, lagged LGN cells, and intercortical inhibition on spatiotemporal processing and direction selectivity

Neural Networks, Год журнала: 2025, Номер 186, С. 107273 - 107273

Опубликована: Фев. 21, 2025

Язык: Английский

---

Cortical determinants of loudness perception and auditory hypersensitivity

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 30, 2024

Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. Here, we observed that activation or inactivation of PVNs functioned like a volume knob in the mouse auditory cortex (ACtx), turning neural behavioral classification sound level up down over 20dB range. PVN loudness adjustments were "sticky", such single bout 40Hz stimulation sustainably suppressed ACtx responsiveness, potentiated feedforward inhibition, behaviorally desensitized mice to loudness. Sensory sensitivity is cardinal feature autism, aging, peripheral neuropathy, prompting us ask whether can persistently desensitize with hyperactivity, hypofunction, hypersensitivity triggered by cochlear sensorineural damage. We found 16-minute session restored normal perception for one week, showing perceptual deficits irreversible injuries be reversed through targeted circuit interventions.

Язык: Английский

---

Cortical direction selectivity increases from the input to the output layers of visual cortex

PLoS Biology, Год журнала: 2025, Номер 23(1), С. e3002947 - e3002947

Опубликована: Янв. 8, 2025

Sensitivity to motion direction is a feature of visual neurons that essential for perception. Recent studies have suggested selectivity re-established at multiple stages throughout the hierarchy, which contradicts traditional assumption in later largely derives from earlier stages. By recording laminar responses areas 17 and 18 anesthetized cats both sexes, we aimed understand how processed relayed across 2 successive stages: input layers output within early cortices. We found strong relationship between strength layers, as well preservation preferred directions layers. Moreover, was enhanced compared with response maintained but reduced other under blank stimuli. identified direction-tuned gain mechanism interlaminar signal transmission, likely originated feedforward connections recurrent This gain, coupled nonlinearity, contributed Our findings suggest cortical partially inherits characteristics further refined by intracortical connections.

Язык: Английский

---