Hearing loss often results in tinnitus and auditory cortical map changes, leading to the prevailing view that the phantom perception is associated with cortical reorganization. However, we show here ...that tinnitus is mediated by a cortical area lacking map reorganization. High-frequency hearing loss results in two distinct cortical regions: a sensory-deprived region characterized by a decrease in inhibitory synaptic transmission and a normal hearing region showing increases in inhibitory and excitatory transmission and map reorganization. Hearing-lesioned animals displayed tinnitus with a pitch in the hearing loss range. Furthermore, drugs that enhance inhibition, but not those that reduce excitation, reversibly eliminated the tinnitus behavior. These results suggest that sensory deprivation-induced homeostatic down-regulation of inhibitory synapses may contribute to tinnitus perception. Enhancing sensory input through map reorganization may plausibly alleviate phantom sensation.
Transient potassium current channels (I
channels), which are expressed in most brain areas, have a central role in modulating feedforward and feedback inhibition along the dendroaxonic axis. Loss of ...the modulatory channels is tightly associated with a number of brain diseases such as Alzheimer's disease, epilepsy, fragile X syndrome (FXS), Parkinson's disease, chronic pain, tinnitus, and ataxia. However, the functional significance of I
channels in these diseases has so far been underestimated. In this review, we discuss the distribution and function of I
channels. Particularly, we posit that downregulation of I
channels results in neuronal (mostly dendritic) hyperexcitability accompanied by the imbalanced excitation and inhibition ratio in the brain's networks, eventually causing the brain diseases. Finally, we propose a potential therapeutic target: the enhanced action of I
channels to counteract Ca
-permeable channels including NMDA receptors could be harnessed to restore dendritic excitability, leading to a balanced neuronal state.
Introduction
The N-methyl-D-aspartate receptor (NMDAR) plays a critical role in synaptic transmission and is associated with various neurological and psychiatric disorders. Recently, a novel form of ...postsynaptic plasticity known as NMDAR-based short-term postsynaptic plasticity (STPP) has been identified. It has been suggested that long-lasting glutamate binding to NMDAR allows for the retention of input information in brain slices up to 500 ms, leading to response facilitation. However, the impact of STPP on the dynamics of neuronal populations remains unexplored.
Methods
In this study, we incorporated STPP into a continuous attractor neural network (CANN) model to investigate its effects on neural information encoding in populations of neurons. Unlike short-term facilitation, a form of presynaptic plasticity, the temporally enhanced synaptic efficacy resulting from STPP destabilizes the network state of the CANN by increasing its mobility.
Results
Our findings demonstrate that the inclusion of STPP in the CANN model enables the network state to predictively respond to a moving stimulus. This nontrivial dynamical effect facilitates the tracking of the anticipated stimulus, as the enhanced synaptic efficacy induced by STPP enhances the system's mobility.
Discussion
The discovered STPP-based mechanism for sensory prediction provides valuable insights into the potential development of brain-inspired computational algorithms for prediction. By elucidating the role of STPP in neural population dynamics, this study expands our understanding of the functional implications of NMDAR-related plasticity in information processing within the brain.
Conclusion
The incorporation of STPP into a CANN model highlights its influence on the mobility and predictive capabilities of neural networks. These findings contribute to our knowledge of STPP-based mechanisms and their potential applications in developing computational algorithms for sensory prediction.
Hearing loss is a major risk factor for tinnitus, hyperacusis, and central auditory processing disorder. Although recent studies indicate that hearing loss causes neuroinflammation in the auditory ...pathway, the mechanisms underlying hearing loss-related pathologies are still poorly understood. We examined neuroinflammation in the auditory cortex following noise-induced hearing loss (NIHL) and its role in tinnitus in rodent models. Our results indicate that NIHL is associated with elevated expression of proinflammatory cytokines and microglial activation-two defining features of neuroinflammatory responses-in the primary auditory cortex (AI). Genetic knockout of tumor necrosis factor alpha (TNF-α) or pharmacologically blocking TNF-α expression prevented neuroinflammation and ameliorated the behavioral phenotype associated with tinnitus in mice with NIHL. Conversely, infusion of TNF-α into AI resulted in behavioral signs of tinnitus in both wild-type and TNF-α knockout mice with normal hearing. Pharmacological depletion of microglia also prevented tinnitus in mice with NIHL. At the synaptic level, the frequency of miniature excitatory synaptic currents (mEPSCs) increased and that of miniature inhibitory synaptic currents (mIPSCs) decreased in AI pyramidal neurons in animals with NIHL. This excitatory-to-inhibitory synaptic imbalance was completely prevented by pharmacological blockade of TNF-α expression. These results implicate neuroinflammation as a therapeutic target for treating tinnitus and other hearing loss-related disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Selective enhancement of GABAergic inhibition is thought to impact many vital brain functions and interferes with the genesis and/or progression of numerous brain disorders. Here, we show that ...selectively increasing NMDA receptor activity in inhibitory neurons using an NMDAR positive allosteric modulator (PAM) elevates spiking activity of inhibitory neurons in vitro and in vivo. In vivo infusion of PAM increases spontaneous and sound-evoked spiking in inhibitory and decreases spiking in excitatory neurons, and increases signal-to-noise ratio in the primary auditory cortex. In addition, PAM infusion prior to noise trauma prevents the occurrence of tinnitus and reduction in GABAergic inhibition. These results reveal that selectively enhancing endogenous NMDAR activity on the GABAergic neurons can effectively enhance inhibitory activity and alter excitatory-inhibitory balance, and may be useful for preventing diseases that involve reduced inhibition as the major cause.
Abstract
Cortical maps, which are indicative of cognitive status, are shaped by the organism’s experience. Previous mapping tools, such as penetrating electrodes and imaging techniques, are limited ...in their ability to be used to assess high-resolution brain maps largely owing to their invasiveness and poor spatiotemporal resolution, respectively. In this study, we developed a flexible graphene-based multichannel electrode array for electrocorticography (ECoG) recording, which enabled us to assess cortical maps in a time- and labor-efficient manner. The flexible electrode array, formed by chemical vapor deposition (CVD)-grown graphene, provided low impedance and electrical noise because a good interface between the graphene and brain tissue was created, which improved the detectability of neural signals. Furthermore, cortical map remodeling was induced upon electrical stimulation at the cortical surface through a subset of graphene spots. This result demonstrated the macroscale plasticity of cortical maps, suggesting perceptual enhancement via electrical rehabilitation at the cortical surface.
Interlamellar CA1 network in the hippocampus Yang, Sunggu; Yang, Sungchil; Moreira, Thais ...
Proceedings of the National Academy of Sciences - PNAS,
09/2014, Letnik:
111, Številka:
35
Journal Article
Recenzirano
Odprti dostop
To understand the cellular basis of learning and memory, the neurophysiology of the hippocampus has been largely examined in thin transverse slice preparations. However, the synaptic architecture ...along the longitudinal septo-temporal axis perpendicular to the transverse projections in CA1 is largely unknown, despite its potential significance for understanding the information processing carried out by the hippocampus. Here, using a battery of powerful techniques, including 3D digital holography and focal glutamate uncaging, voltage-sensitive dye, two-photon imaging, electrophysiology, and immunohistochemistry, we show that CA1 pyramidal neurons are connected to one another in an associational and well-organized fashion along the longitudinal axis of the hippocampus. Such CA1 longitudinal connections mediate reliable signal transfer among the pyramidal cells and express significant synaptic plasticity. These results illustrate a need to reconceptualize hippocampal CA1 network function to include not only processing in the transverse plane, but also operations made possible by the longitudinal network. Our data will thus provide an essential basis for future computational modeling studies on information processing operations carried out in the full 3D hippocampal network that underlies its complex cognitive functions.
Abstract
Various electrophysiological and imaging techniques have been studied for the diagnosis and treatment of epilepsy. In particular, electrocorticography (ECoG) provides valuable information ...that can guide clinical treatment of patients with epilepsy. Currently, it is necessary to define the clinical benefits of ECoG in free-moving animals for the treatment of epilepsy. Here, we present the results of simultaneous recordings of multiple cortical sites and responsive neurostimulations for epilepsy treatment carried out in free-moving rats. In this study, we developed a high-density, flexible electrode array comprising graphene/Au/graphene that stably wraps onto the cortex surface of a living rat brain, exhibiting a superior signal-to-noise ratio. The hybrid graphene multichannel electrode successfully detected brain signals with high-throughput spatiotemporal resolution and substantially suppressed pilocarpine-induced epileptic discharges and behavior. Simultaneous recording and neurostimulation in awake animals can lead to a fundamental change in the treatment of medically intractable epilepsy.
Longitudinal synaptic connections between dentate gyrus (DG) granule neurons in the hippocampus have been found to be correlated with increased anxiety. Here, we present a protocol to assess synaptic ...connectivity and plasticity in the longitudinal DG network. We detail the steps for (1) obtaining acute mouse hippocampal slices that contain longitudinal DG-DG connections, (2) measuring excitatory postsynaptic potentials using whole-cell patch clamp recording combined with two-photon microscopy and glutamate uncaging, and (3) assessing synaptic plasticity using extracellular field recording.
For complete details on the use and execution of this protocol, please refer to Pak et al. (2022).1
Display omitted
•Obtain healthy hippocampal slices that contain intact DG-DG longitudinal synapses•Measure postsynaptic membrane potential in whole-cell patched DG granule cells (DGGCs)•Induce EPSPs in patched DGGCs using two-photon microscopy and glutamate uncaging•Measure synaptic plasticity of DG-DG synapses using extracellular field recording
Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Longitudinal synaptic connections between dentate gyrus (DG) granule neurons in the hippocampus have been found to be correlated with increased anxiety. Here, we present a protocol to assess synaptic connectivity and plasticity in the longitudinal DG network. We detail the steps for (1) obtaining acute mouse hippocampal slices that contain longitudinal DG-DG connections, (2) measuring excitatory postsynaptic potentials using whole-cell patch clamp recording combined with two-photon microscopy and glutamate uncaging, and (3) assessing synaptic plasticity using extracellular field recording.
The hypothalamic arcuate nucleus (Arc) is a central unit that controls the appetite through the integration of metabolic, hormonal, and neuronal afferent inputs. Agouti-related protein (AgRP), ...proopiomelanocortin (POMC), and dopaminergic neurons in the Arc differentially regulate feeding behaviors in response to hunger, satiety, and appetite, respectively. At the time of writing, the anatomical and electrophysiological characterization of these three neurons has not yet been intensively explored. Here, we interrogated the overall characterization of AgRP, POMC, and dopaminergic neurons using genetic mouse models, immunohistochemistry, and whole-cell patch recordings. We identified the distinct geographical location and intrinsic properties of each neuron in the Arc with the transgenic lines labelled with cell-specific reporter proteins. Moreover, AgRP, POMC, and dopaminergic neurons had different firing activities to ghrelin and leptin treatments. Ghrelin led to the increased firing rate of dopaminergic and AgRP neurons, and the decreased firing rate of POMC. In sharp contrast, leptin resulted in the decreased firing rate of AgRP neurons and the increased firing rate of POMC neurons, while it did not change the firing rate of dopaminergic neurons in Arc. These findings demonstrate the anatomical and physiological uniqueness of three hypothalamic Arc neurons to appetite control.
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