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

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Cellular, synaptic, and network effects of chemokines in the central nervous system and their implications to behavior

Pharmacological Reports, Год журнала: 2021, Номер 73(6), С. 1595 - 1625

Опубликована: Авг. 26, 2021

Abstract Accumulating evidence highlights chemokines as key mediators of the bidirectional crosstalk between neurons and glial cells aimed at preserving brain functioning. The multifaceted role these immune proteins in CNS is mirrored by complexity mechanisms underlying its biological function, including biased signaling. Neurons, only concert with cells, are essential players modulation homeostatic functions. Yet, attempts to dissect complex multilevel coordination still lacking. Therefore, purpose this review summarize current knowledge about chemokine regulation neuron–glia linking molecular, cellular, network, behavioral levels. Following a brief description molecular which interact their receptors then summarizing cellular patterns expression CNS, we next delve into sequence chemokine-regulated communication context neuroprotection. We define interactions other neurotransmitters, neuromodulators, gliotransmitters. Finally, describe fine-tuning on network level relevance modulation. believe that better understanding nature events drive neuro-glial holds promise for development new treatment strategies could, context- time-dependent manner, modulate action specific promote repair reduce neurological impairment.

Язык: Английский

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Integrins Bidirectionally Regulate the Efficacy of Inhibitory Synaptic Transmission and Control GABAergic Plasticity

Journal of Neuroscience, Год журнала: 2022, Номер 42(30), С. 5830 - 5842

Опубликована: Июнь 14, 2022

For many decades, synaptic plasticity was believed to be restricted excitatory transmission. However, in recent years, this view started change, and now it is recognized that GABAergic synapses show distinct forms of activity-dependent long-term plasticity, but the underlying mechanisms remain obscure. Herein, we asked whether signaling mediated by β1 or β3 subunit-containing integrins might involved regulating efficacy synapses, including NMDA receptor-dependent inhibitory potentiation (iLTP) hippocampus. We found activation integrin with fibrinogen induced a stable depression, whereas inhibition potentiated at CA1 pyramidal neurons male mice. Additionally, compounds interfere interaction extracellular matrix blocked induction NMDA-iLTP. In conclusion, provide first evidence are key players endogenous modulatory SIGNIFICANCE STATEMENT Epilepsy, schizophrenia, anxiety just few medical conditions associated dysfunctional known for their extraordinary susceptibility modulation factors exogenous pharmacological agents. describe here integrins, adhesion proteins, play role Specifically, interference integrin-dependent results variety effects on amplitude frequency mIPSCs. Activation induces iLTP. Our unveil an important mechanism controlling inhibition, which opens new avenues into usage integrin-aimed pharmaceuticals as modulators synapses.

Язык: Английский

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Dissociated Representation of Binaural Cues in Single-Sided Deafness: Implications for Cochlear Implantation

Journal of Neuroscience, Год журнала: 2024, Номер 44(28), С. e1653232024 - e1653232024

Опубликована: Июнь 3, 2024

Congenital single-sided deafness (SSD) leads to an aural preference syndrome that is characterized by overrepresentation of the hearing ear in auditory system. Cochlear implantation (CI) deaf effective treatment for SSD. However, newly introduced input congenital SSD often does not reach expectations late-implanted CI recipients with respect binaural and speech perception. In a previous study, reduction interaural time difference (ITD) sensitivity has been shown unilaterally congenitally cats (uCDCs). present we focused on level (ILD) processing primary cortex. The uCDC group was compared (HCs) bilaterally (CDCs). ILD representation reorganized, replacing contralateral ear, regardless cortical hemisphere. accordance uCDCs were less sensitive differences than HCs, resulting unmodulated ITD responses, thus lacking directional information. Such incongruent ITDs ILDs cannot be integrated sound source localization. normal hearing, predominant effect each excitation cortex hemisphere inhibition ipsilateral SSD, however, pathways reorganized such produced greater both hemispheres weaker preserved hemispheres.

Язык: Английский

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Pleiotropic neurotransmitters: neurotransmitter-receptor crosstalk regulates excitation-inhibition balance in social brain functions and pathologies

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Март 14, 2025

Neuronal excitation-inhibition (E/I) balance is essential for maintaining neuronal stability and proper brain functioning. Disruptions in this are implicated various neurological disorders, including autism spectrum disorder, schizophrenia epilepsy. The E/I thought to be primarily mediated by intrinsic excitability, governed an array of voltage-gated ion channels, extrinsic maintained through a counterbalance between excitatory synaptic transmission transmitter glutamate acting on ion-tropic receptors inhibitory transmissions chiefly GABA or glycine their respective receptors. However, recent studies reveal that neurotransmitters can exhibit interactions extend beyond traditional targets, leading phenomenon called neurotransmitter-receptor crosstalk. Examples such crosstalks include earlier discovery functioning as co-transmitter gating the NMDA subtype receptor, most demonstration shows binds GABAA thereby allosterically potentiating its function. These demonstrate structurally physiologically important crosstalk transmission, blurring distinction concepts classic transmission. In article, evidence supporting forms will briefly summarized underlying mechanisms discussed. Furthermore, review discuss implications these balance, well potential involvement plasticity cognition context social conditions.

Язык: Английский

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