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Introduction: The emergent coherent population activity from thousands of stochastic neurons in the brain is believed to constitute a key neuronal mechanism for salient processing of external stimuli and its link to internal states like attention and perception. In the sensory cortex, functional cell assemblies are formed by recurrent excitation and inhibitory influences. The stochastic dynamics of each cell involved is largely orchestrated by presynaptic CAV2.1 voltage-gated calcium channels (VGCCs). Cav2.1 VGCCs initiate the release of neurotransmitters from the presynaptic compartment and are therefore able to add variability into synaptic transmission which can be partly explained by their mobile organization around docked vesicles. Methods: To investigate the relevance of Cav2.1 channel surface motility for the input processing in the primary auditory cortex (A1) in vivo, we make use of a new optogenetic system which allows for acute, reversable cross-linking Cav2.1 VGCCs via a photo-cross-linkable cryptochrome mutant, CRY2olig. In order to map neuronal activity across all cortical layers of the A1, we performed laminar current-source density (CSD) recordings with varying auditory stimulus sets in transgenic mice with a citrine tag on the N-terminus of the VGCCs. Results: Clustering VGCCs suppresses overall sensory-evoked population activity, particularly when stimuli lead to a highly synchronized distribution of synaptic inputs. Discussion: Our findings reveal the importance of membrane dynamics of presynaptic calcium channels for sensory encoding by dynamically adjusting network activity across a wide range of synaptic input strength.
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Distinguishing between regular and irregular heartbeats, conversing with speakers of different accents, and tuning a guitar-all rely on some form of auditory learning. What drives these experience-dependent changes? A growing body of evidence suggests an important role for non-sensory influences, including reward, task engagement, and social or linguistic context. This review is a collection of contributions that highlight how these non-sensory factors shape auditory plasticity and learning at the molecular, physiological, and behavioral level. We begin by presenting evidence that reward signals from the dopaminergic midbrain act on cortico-subcortical networks to shape sound-evoked responses of auditory cortical neurons, facilitate auditory category learning, and modulate the long-term storage of new words and their meanings. We then discuss the role of task engagement in auditory perceptual learning and suggest that plasticity in top-down cortical networks mediates learning-related improvements in auditory cortical and perceptual sensitivity. Finally, we present data that illustrates how social experience impacts sound-evoked activity in the auditory midbrain and forebrain and how the linguistic environment rapidly shapes speech perception. These findings, which are derived from both human and animal models, suggest that non-sensory influences are important regulators of auditory learning and plasticity and are often implemented by shared neural substrates. Application of these principles could improve clinical training strategies and inform the development of treatments that enhance auditory learning in individuals with communication disorders.
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Corteza Auditiva , Plasticidad Neuronal , Animales , Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Plasticidad Neuronal/fisiologíaRESUMEN
Corticofugal projections outnumber subcortical input projections by far. However, the specific role for signal processing of corticofugal feedback is still less well understood in comparisonto the feedforward projection. Here, we lesioned corticothalamic (CT) neurons in layers V and/or VI of the auditory cortex of Mongolian gerbils by laser-induced photolysis to investigate their contribution to cortical activation patterns. We have used laminar current-source density (CSD) recordings of tone-evoked responses and could show that, particularly, lesion of CT neurons in layer VI affected cortical frequency processing. Specifically, we found a decreased gain of best-frequency input in thalamocortical (TC)-recipient input layers that correlated with the relative lesion of layer VI neurons, but not layer V neurons. Using cortical silencing with the GABA a -agonist muscimol and layer-specific intracortical microstimulation (ICMS), we found that direct activation of infragranular layers recruited a local recurrent cortico-thalamo-cortical loop of synaptic input. This recurrent feedback was also only interrupted when lesioning layer VI neurons, but not cells in layer V. Our study thereby shows distinct roles of these two types of CT neurons suggesting a particular impact of CT feedback from layer VI to affect the local feedforward frequency processing in auditory cortex.
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Apoptosis/fisiología , Corteza Auditiva/fisiología , Retroalimentación Fisiológica/fisiología , Rayos Láser/efectos adversos , Neuronas/fisiología , Tálamo/fisiología , Estimulación Acústica/métodos , Animales , Apoptosis/efectos de los fármacos , Corteza Auditiva/efectos de los fármacos , Corteza Auditiva/patología , Retroalimentación Fisiológica/efectos de los fármacos , Agonistas de Receptores de GABA-A/farmacología , Gerbillinae , Masculino , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/patología , Vías Nerviosas/fisiología , Neuronas/efectos de los fármacos , Neuronas/patología , Tálamo/efectos de los fármacos , Tálamo/patologíaRESUMEN
Hearing deficits impact on the communication with the external world and severely compromise perception of the surrounding. Deafness can be caused by particular mutations in the neuroplastin (Nptn) gene, which encodes a transmembrane recognition molecule of the immunoglobulin (Ig) superfamily and plasma membrane Calcium ATPase (PMCA) accessory subunit. This study investigates whether the complete absence of neuroplastin or the loss of neuroplastin in the adult after normal development lead to hearing impairment in mice analyzed by behavioral, electrophysiological, and in vivo imaging measurements. Auditory brainstem recordings from adult neuroplastin-deficient mice (Nptn-/-) show that these mice are deaf. With age, hair cells and spiral ganglion cells degenerate in Nptn-/- mice. Adult Nptn-/- mice fail to behaviorally respond to white noise and show reduced baseline blood flow in the auditory cortex (AC) as revealed by single-photon emission computed tomography (SPECT). In adult Nptn-/- mice, tone-evoked cortical activity was not detectable within the primary auditory field (A1) of the AC, although we observed non-persistent tone-like evoked activities in electrophysiological recordings of some young Nptn-/- mice. Conditional ablation of neuroplastin in Nptnlox/loxEmx1Cre mice reveals that behavioral responses to simple tones or white noise do not require neuroplastin expression by central glutamatergic neurons. Loss of neuroplastin from hair cells in adult NptnΔlox/loxPrCreERT mice after normal development is correlated with increased hearing thresholds and only high prepulse intensities result in effective prepulse inhibition (PPI) of the startle response. Furthermore, we show that neuroplastin is required for the expression of PMCA 2 in outer hair cells. This suggests that altered Ca2+ homeostasis underlies the observed hearing impairments and leads to hair cell degeneration. Our results underline the importance of neuroplastin for the development and the maintenance of the auditory system.
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Audición , Animales , Umbral Auditivo , Potenciales Evocados Auditivos del Tronco Encefálico , Pérdida Auditiva , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , ATPasas Transportadoras de Calcio de la Membrana Plasmática/metabolismoRESUMEN
In the adult vertebrate brain, enzymatic removal of the extracellular matrix (ECM) is increasingly recognized to promote learning, memory recall, and restorative plasticity. The impact of the ECM on translaminar dynamics during cortical circuit processing is still not understood. Here, we removed the ECM in the primary auditory cortex (ACx) of adult Mongolian gerbils using local injections of hyaluronidase (HYase). Using laminar current-source density (CSD) analysis, we found layer-specific changes of the spatiotemporal synaptic patterns with increased cross-columnar integration and simultaneous weakening of early local sensory input processing within infragranular layers Vb. These changes had an oscillatory fingerprint within beta-band (25-36 Hz) selectively within infragranular layers Vb. To understand the laminar interaction dynamics after ECM digestion, we used time-domain conditional Granger causality (GC) measures to identify the increased drive of supragranular layers towards deeper infragranular layers. These results showed that ECM degradation altered translaminar cortical network dynamics with a stronger supragranular lead of the columnar response profile.
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Corteza Auditiva/fisiología , Percepción Auditiva , Potenciales Evocados Auditivos , Matriz Extracelular/fisiología , Animales , Corteza Auditiva/efectos de los fármacos , Corteza Auditiva/metabolismo , Vías Auditivas/fisiología , Percepción Auditiva/efectos de los fármacos , Potenciales Evocados Auditivos/efectos de los fármacos , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Gerbillinae , Audición , Hialuronoglucosaminidasa/administración & dosificación , Inyecciones , Masculino , Factores de TiempoRESUMEN
The primary auditory cortex (A1) is an essential, integrative node that encodes the behavioral relevance of acoustic stimuli, predictions, and auditory-guided decision-making. However, the realization of this integration with respect to the cortical microcircuitry is not well understood. Here, we characterize layer-specific, spatiotemporal synaptic population activity with chronic, laminar current source density analysis in Mongolian gerbils (Meriones unguiculatus) trained in an auditory decision-making Go/NoGo shuttle-box task. We demonstrate that not only sensory but also task- and choice-related information is represented in the mesoscopic neuronal population code of A1. Based on generalized linear-mixed effect models we found a layer-specific and multiplexed representation of the task rule, action selection, and the animal's behavioral options as accumulating evidence in preparation of correct choices. The findings expand our understanding of how individual layers contribute to the integrative circuit in the sensory cortex in order to code task-relevant information and guide sensory-based decision-making.
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Estimulación Acústica , Corteza Auditiva/fisiología , Percepción Auditiva , Potenciales Evocados Auditivos , Gerbillinae/fisiología , Análisis y Desempeño de Tareas , Animales , Conducta Animal , MasculinoRESUMEN
KEY POINTS: Ketamine is a common anaesthetic agent used in research and more recently as medication in treatment of depression. It has known effects on inhibition of interneurons and cortical stimulus-locked responses, but the underlying functional network mechanisms are still elusive. Analysing population activity across all layers within the auditory cortex, we found that doses of this anaesthetic induce a stronger activation and stimulus-locked response to pure-tone stimuli. This cortical response is driven by gain enhancement of thalamocortical input processing selectively within granular layers due to an increased recurrent excitation. Time-frequency analysis indicates a higher broadband magnitude response and prolonged phase coherence in granular layers, possibly pointing to disinhibition of this recurrent excitation. These results further the understanding of ketamine's functional mechanisms, which will improve the ability to interpret physiological studies moving from anaesthetized to awake paradigms and may lead to the development of better ketamine-based depression treatments with lower side effects. ABSTRACT: Ketamine is commonly used as an anaesthetic agent and has more recently gained attention as an antidepressant. It has been linked to increased stimulus-locked excitability, inhibition of interneurons and modulation of intrinsic neuronal oscillations. However, the functional network mechanisms are still elusive. A better understanding of these anaesthetic network effects may improve upon previous interpretations of seminal studies conducted under anaesthesia and have widespread relevance for neuroscience with awake and anaesthetized subjects as well as in medicine. Here, we investigated the effects of anaesthetic doses of ketamine (15 mg kg-1 h-1 i.p.) on the network activity after pure-tone stimulation within the auditory cortex of male Mongolian gerbils (Meriones unguiculatus). We used laminar current source density (CSD) analysis and subsequent layer-specific continuous wavelet analysis to investigate spatiotemporal response dynamics on cortical columnar processing in awake and ketamine-anaesthetized animals. We found thalamocortical input processing within granular layers III/IV to be significantly increased under ketamine. This layer-dependent gain enhancement under ketamine was not due to changes in cross-trial phase coherence but was rather attributed to a broadband increase in magnitude reflecting an increase in recurrent excitation. A time-frequency analysis was indicative of a prolonged period of stimulus-induced excitation possibly due to a reduced coupling of excitation and inhibition in granular input circuits - in line with the common hypothesis of cortical disinhibition via suppression of GABAergic interneurons.
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Anestesia , Corteza Auditiva , Ketamina , Animales , Gerbillinae , Humanos , Ketamina/farmacología , Masculino , NeuronasRESUMEN
In the brain, Hebbian-type and homeostatic forms of plasticity are affected by neuromodulators like dopamine (DA). Modifications of the perisynaptic extracellular matrix (ECM), which control the functions and mobility of synaptic receptors as well as the diffusion of transmitters and neuromodulators in the extracellular space, are crucial for the manifestation of plasticity. Mechanistic links between synaptic activation and ECM modifications are largely unknown. Here, we report that neuromodulation via D1-type DA receptors can induce targeted ECM proteolysis specifically at excitatory synapses of rat cortical neurons via proteases ADAMTS-4 and -5. We showed that receptor activation induces increased proteolysis of brevican (BC) and aggrecan, two major constituents of the adult ECM both in vivo and in vitro. ADAMTS immunoreactivity was detected near synapses, and shRNA-mediated knockdown reduced BC cleavage. We have outlined a molecular scenario of how synaptic activity and neuromodulation are linked to ECM rearrangements via increased cAMP levels, NMDA receptor activation, and intracellular calcium signaling.
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Matriz Extracelular/metabolismo , Terminales Presinápticos/metabolismo , Receptores Dopaminérgicos/metabolismo , Sinapsis/metabolismo , Proteínas ADAMTS/metabolismo , Animales , Brevicano/metabolismo , Canales de Calcio Tipo L/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Células Cultivadas , AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Furina/metabolismo , Proteínas de Andamiaje Homer/metabolismo , Activación del Canal Iónico , Masculino , Corteza Prefrontal/metabolismo , Ratas Wistar , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
Harmful environmental sounds are a prevailing source of chronic hearing impairments, including noise induced hearing loss, hyperacusis, or tinnitus. How these symptoms are related to pathophysiological damage to the sensory receptor epithelia and its effects along the auditory pathway, have been documented in numerous studies. An open question concerns the temporal evolution of maladaptive changes after damage and their manifestation in the balance of thalamocortical and corticocortical input to the auditory cortex (ACx). To address these issues, we investigated the loci of plastic reorganizations across the tonotopic axis of the auditory cortex of male Mongolian gerbils (Meriones unguiculatus) acutely after a sound trauma and after several weeks. We used a residual current-source density analysis to dissociate adaptations of intracolumnar input and horizontally relayed corticocortical input to synaptic populations across cortical layers in ACx. A pure tone-based sound trauma caused acute changes of subcortical inputs and corticocortical inputs at all tonotopic regions, particularly showing a broad reduction of tone-evoked inputs at tonotopic regions around the trauma frequency. At other cortical sites, the overall columnar activity acutely decreased, while relative contributions of lateral corticocortical inputs increased. After 4-6 weeks, cortical activity in response to the altered sensory inputs showed a general increase of local thalamocortical input reaching levels higher than before the trauma. Hence, our results suggest a detailed mechanism for overcompensation of altered frequency input in the auditory cortex that relies on a changing balance of thalamocortical and intracortical input and along the frequency gradient of the cortical tonotopic map.
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Cortical release of the neurotransmitter dopamine has been implied in adapting cortical processing with respect to various functions including coding of stimulus salience, expectancy, error prediction, behavioral relevance and learning. Dopamine agonists have been shown to modulate recurrent cortico-thalamic feedback, and should therefore also affect synchronization and amplitude of thalamo-cortical oscillations. In this study, we have used multitaper spectral and time-frequency analysis of stimulus-evoked and spontaneous current source density patterns in primary auditory cortex of Mongolian gerbils to characterize dopaminergic neuromodulation of the oscillatory structure of current sources and sinks. We systemically applied D1/D5-receptor agonist SKF-38393 followed by competitive D1/D5-receptor antagonist SCH-23390. Our results reveal an increase in stimulus phase-locking in the high gamma-band (88-97 Hz) by SKF-38393, specifically in layers III/IV at the best frequency, which occurred at 20 ms after tone onset, and was reversed by SCH-23390. However, changes in induced oscillatory power after SKF-38393 treatment occurred stimulus-independently in the background activity in different layers than phase-locking effects and were not reversed by SCH-23390. These effects might either reflect longer-lasting changes in neural background noise, non-specific changes due to ketamine anesthesia, or an interaction of both. Without concomitant stimulus-induced power increase, increased stimulus phase-locking in layers III/IV indicates enhanced phase-resetting of neural oscillations by the stimulus after D1/D5-receptor activation. The frequency characteristics, together with the demonstrated stimulus specificity and layer specificity, suggest that changes in phase-resetting originate from dopaminergic neuromodulation of thalamo-cortical interactions. Enhanced phase-resetting might be a key step in the recruitment of cortical activity modes interpreting sensory input.
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Corteza Auditiva , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Animales , Dopamina , Gerbillinae , Receptores de Dopamina D1RESUMEN
It is a daily challenge for our brains to establish new memories via learning while providing stable storage of remote memories. In the adult vertebrate brain, bimodal regulation of the extracellular matrix (ECM) may regulate the delicate balance of learning-dependent plasticity and stable memory formation. Here, we trained adult male mice in a cortex-dependent auditory discrimination task and measured the abundance of ECM proteins brevican (BCN) and tenascin-R over the course of acquisition learning, consolidation, and long-term recall in two learning-relevant brain regions; the auditory cortex and hippocampus. Although early training led to a general downregulation of total ECM proteins, successful retrieval correlated with a region-specific and transient upregulation of BCN levels in the auditory cortex. No other parameter such as arousal or stress could account for the transient and region-specific BCN upregulation. This performance-dependent biphasic regulation of the ECM may assist transient plasticity to facilitate initial learning and subsequently promote the long-term consolidation of memory.SIGNIFICANCE STATEMENT The capacity to learn throughout life and at the same time guarantee lifelong storage and remote recall of established memories is a daily challenge. Emerging evidence suggests an important function of the extracellular matrix (ECM), a conglomerate of secreted proteins and polysaccharides in the adult vertebrate brain. We trained mice in an auditory long-term memory task and measured learning-related dynamic changes of the ECM protein brevican. Specifically, in the auditory cortex brevican is downregulated during initial learning and subsequently upregulated in exclusively those animals that have learned the task, suggesting a performance-dependent regulation in the service of memory consolidation and storage. Our data may provide novel therapeutic implications for several neuropsychiatric diseases involving dysregulation of the ECM.
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Corteza Auditiva/metabolismo , Brevicano/genética , Consolidación de la Memoria , Animales , Corteza Auditiva/fisiología , Percepción Auditiva , Brevicano/metabolismo , Discriminación en Psicología , Hipocampo/metabolismo , Hipocampo/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Regulación hacia ArribaRESUMEN
Reward associations during auditory learning induce cortical plasticity in the primary auditory cortex. A prominent source of such influence is the ventral tegmental area (VTA), which conveys a dopaminergic teaching signal to the primary auditory cortex. Yet, it is unknown, how the VTA influences cortical frequency processing and spectral integration. Therefore, we investigated the temporal effects of direct optogenetic stimulation of the VTA onto spectral integration in the auditory cortex on a synaptic circuit level by current-source-density analysis in anesthetized Mongolian gerbils. While auditory lemniscal input predominantly terminates in the granular input layers III/IV, we found that VTA-mediated modulation of spectral processing is relayed by a different circuit, namely enhanced thalamic inputs to the infragranular layers Vb/VIa. Activation of this circuit yields a frequency-specific gain amplification of local sensory input and enhances corticocortical information transfer, especially in supragranular layers I/II. This effects persisted over more than 30 minutes after VTA stimulation. Altogether, we demonstrate that the VTA exhibits a long-lasting influence on sensory cortical processing via infragranular layers transcending the signaling of a mere reward-prediction error. We thereby demonstrate a cellular and circuit substrate for the influence of reinforcement-evaluating brain systems on sensory processing in the auditory cortex.
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Corteza Auditiva/fisiología , Tálamo/fisiología , Área Tegmental Ventral/fisiología , Estimulación Acústica , Animales , Gerbillinae , Masculino , Vías Nerviosas/fisiología , Neuronas/fisiología , OptogenéticaRESUMEN
Feedback signals from the primary auditory cortex (A1) can shape the receptive field properties of neurons in the ventral division of the medial geniculate body (MGBv). However, the behavioral significance of corticothalamic modulation is unknown. The aim of this study was to elucidate the role of this descending pathway in the perception of complex sounds. We tested the ability of adult female ferrets to detect the presence of a mistuned harmonic in a complex tone using a positive conditioned go/no-go behavioral paradigm before and after the input from layer VI in A1 to MGBv was bilaterally and selectively eliminated using chromophore-targeted laser photolysis. MGBv neurons were identified by their short latencies and sharp tuning curves. They responded robustly to harmonic complex tones and exhibited an increase in firing rate and temporal pattern changes when one frequency component in the complex tone was mistuned. Injections of fluorescent microbeads conjugated with a light-sensitive chromophore were made in MGBv, and, following retrograde transport to the cortical cell bodies, apoptosis was induced by infrared laser illumination of A1. This resulted in a selective loss of â¼60% of layer VI A1-MGBv neurons. After the lesion, mistuning detection was impaired, as indicated by decreased d' values, a shift of the psychometric curves toward higher mistuning values, and increased thresholds, whereas discrimination performance was unaffected when level cues were also available. Our results suggest that A1-MGBv corticothalamic feedback contributes to the detection of harmonicity, one of the most important grouping cues in the perception of complex sounds.SIGNIFICANCE STATEMENT Perception of a complex auditory scene is based on the ability of the brain to group those sound components that belong to the same source and to segregate them from those belonging to different sources. Because two people talking simultaneously may differ in their voice pitch, perceiving the harmonic structure of sounds is very important for auditory scene analysis. Here we demonstrate mistuning sensitivity in the thalamus and that feedback from the primary auditory cortex is required for the normal ability of ferrets to detect a mistuned harmonic within a complex sound. These results provide novel insight into the function of descending sensory pathways in the brain and suggest that this corticothalamic circuit plays an important role in scene analysis.
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Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Retroalimentación Fisiológica/fisiología , Hurones/fisiología , Tálamo/fisiología , Estimulación Acústica , Animales , Corteza Auditiva/citología , Corteza Auditiva/diagnóstico por imagen , Umbral Auditivo/fisiología , Conducta Animal/fisiología , Señales (Psicología) , Discriminación en Psicología/fisiología , Femenino , Cuerpos Geniculados/fisiología , Sonido , Tálamo/citología , Tálamo/diagnóstico por imagenRESUMEN
Robust perception of auditory objects over a large range of sound intensities is a fundamental feature of the auditory system. However, firing characteristics of single neurons across the entire auditory system, like the frequency tuning, can change significantly with stimulus intensity. Physiological correlates of level-constancy of auditory representations hence should be manifested on the level of larger neuronal assemblies or population patterns. In this study we have investigated how information of frequency and sound level is integrated on the circuit-level in the primary auditory cortex (AI) of the Mongolian gerbil. We used a combination of pharmacological silencing of corticocortically relayed activity and laminar current source density (CSD) analysis. Our data demonstrate that with increasing stimulus intensities progressively lower frequencies lead to the maximal impulse response within cortical input layers at a given cortical site inherited from thalamocortical synaptic inputs. We further identified a temporally precise intercolumnar synaptic convergence of early thalamocortical and horizontal corticocortical inputs. Later tone-evoked activity in upper layers showed a preservation of broad tonotopic tuning across sound levels without shifts towards lower frequencies. Synaptic integration within corticocortical circuits may hence contribute to a level-robust representation of auditory information on a neuronal population level in the auditory cortex.
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Estimulación Acústica , Corteza Auditiva/fisiología , Potenciales Evocados Auditivos/fisiología , Algoritmos , Animales , Vías Auditivas/fisiología , Percepción Auditiva/fisiología , Mapeo Encefálico , Gerbillinae , Masculino , Neuronas/fisiología , Sonido , Transmisión SinápticaRESUMEN
The harmonic structure of sounds is an important grouping cue in auditory scene analysis. The ability of ferrets to detect mistuned harmonics was measured using a go/no-go task paradigm. Psychometric functions plotting sensitivity as a function of degree of mistuning were used to evaluate behavioral performance using signal detection theory. The mean (± standard error of the mean) threshold for mistuning detection was 0.8 ± 0.1 Hz, with sensitivity indices and reaction times depending on the degree of mistuning. These data provide a basis for investigation of the neural basis for the perception of complex sounds in ferrets, an increasingly used animal model in auditory research.
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Percepción Auditiva , Conducta Animal , Señales (Psicología) , Hurones/psicología , Actividad Motora , Detección de Señal Psicológica , Estimulación Acústica , Animales , Vías Auditivas/fisiología , Femenino , Hurones/fisiología , Psicoacústica , Tiempo de Reacción , Factores de TiempoRESUMEN
We have learned to detect, predict and behaviorally respond to important changes in our environment on short and longer time scales. Therefore, brains of humans and higher animals build upon a perceptual and semantic salience stored in their memories mainly generated by associative reinforcement learning. Functionally, the brain needs to extract and amplify a small number of features of sensory input with behavioral relevance to a particular situation in order to guide behavior. In this review, I argue that dopamine action, particularly in sensory cortex, orchestrates layer-dependent local and long-range cortical circuits integrating sensory associated bottom-up and semantically relevant top-down information, respectively. Available evidence reveals that dopamine thereby controls both the selection of perceptually or semantically salient signals as well as feedback processing from higher-order areas in the brain. Sensory cortical dopamine thereby governs the integration of selected sensory information within a behavioral context. This review proposes that dopamine enfolds this function by temporally distinct actions on particular layer-dependent local and global cortical circuits underlying the integration of sensory, and non-sensory cognitive and behavioral variables.
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Encéfalo/metabolismo , Dopamina/metabolismo , Aprendizaje/fisiología , Animales , Conducta , Corteza Cerebral/citología , Corteza Cerebral/fisiología , Retroalimentación , Humanos , Neuronas/citología , Neuronas/fisiologíaRESUMEN
Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species. Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).
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Corteza Auditiva/fisiología , Reacción de Prevención/fisiología , Percepción/fisiología , Animales , Condicionamiento Clásico , Estimulación Eléctrica/métodos , Gerbillinae , MasculinoRESUMEN
In this study, we describe differences between neural plasticity in auditory cortex (AC) of animals that developed subjective tinnitus (group T) after noise-induced hearing loss (NIHL) compared to those that did not [group non-tinnitus (NT)]. To this end, our analysis focuses on the input activity of cortical neurons based on the temporal and spectral analysis of local field potential (LFP) recordings and an in-depth analysis of auditory brainstem responses (ABR) in the same animals. In response to NIHL in NT animals we find a significant general reduction in overall cortical activity and spectral power as well as changes in all ABR wave amplitudes as a function of loudness. In contrast, T-animals show no significant change in overall cortical activity as assessed by root mean square analysis of LFP amplitudes, but a specific increase in LFP spectral power and in the amplitude of ABR wave V reflecting activity in the inferior colliculus (IC). Based on these results, we put forward a refined model of tinnitus prevention after NIHL that acts via a top-down global (i.e., frequency-unspecific) inhibition reducing overall neuronal activity in AC and IC, thereby counteracting NIHL-induced bottom-up frequency-specific neuroplasticity suggested in current models of tinnitus development.
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Motivated by the increasing evidence that auditory cortex is under control of dopaminergic cell structures of the ventral midbrain, we studied how the ventral tegmental area and substantia nigra affect neuronal activity in auditory cortex. We electrically stimulated 567 deep brain sites in total within and in the vicinity of the two dopaminergic ventral midbrain structures and at the same time, recorded local field potentials and neuronal discharges in cortex. In experiments conducted on three awake macaque monkeys, we found that electrical stimulation of the dopaminergic ventral midbrain resulted in short-latency (~35 ms) phasic activations in all cortical layers of auditory cortex. We were also able to demonstrate similar activations in secondary somatosensory cortex and superior temporal polysensory cortex. The electrically evoked responses in these parts of sensory cortex were similar to those previously described for prefrontal cortex. Moreover, these phasic responses could be reversibly altered by the dopamine D1-receptor antagonist SCH23390 for several tens of minutes. Thus, we speculate that the dopaminergic ventral midbrain exerts a temporally precise, phasic influence on sensory cortex using fast-acting non-dopaminergic transmitters and that their effects are modulated by dopamine on a longer timescale. Our findings suggest that some of the information carried by the neuronal discharges in the dopaminergic ventral midbrain, such as the motivational value or the motivational salience, is transmitted to auditory cortex and other parts of sensory cortex. The mesocortical pathway may thus contribute to the representation of non-auditory events in the auditory cortex and to its associative functions.