Spectral breadth and laminar distribution of thalamocortical inputs to A1

The GABAergic agonist muscimol is used to inactivate brain regions in order to reveal afferent inputs in isolation. However, muscimol's use in primary auditory cortex (A1) has been questioned on the grounds that it may unintentionally suppress thalamocortical inputs. We tested whether muscimol can preferentially suppress cortical, but not thalamocortical, circuits in urethane-anesthetized mice. We recorded tone-evoked current source density profiles to determine frequency receptive fields (RFs) for three current sinks: the “layer 4” sink (fastest onset, middle-layer sink) and current sinks 100 μm above (“layer 2/3”) and 300 μm below (“layer 5/6”) the main input. We first determined effects of muscimol dose (0.01–1 mM) on the characteristic frequency (CF) tone-evoked layer 4 sink. An “ideal” dose (100 μM) had no effect on CF-evoked sink onset latency or initial response but reduced peak amplitude by >80%, implying inhibition of intracortical, but not thalamocortical, activity. We extended the analysis to current sinks in layers 2/3 and 5/6 and for all three sinks determined RF breadth (quarter-octave steps, 20 dB above CF threshold). Muscimol reduced RF breadth 42% in layer 2/3 (from 2.4 ± 0.14 to 1.4 ± 0.11 octaves), 14% in layer 4 (2.2 ± 0.12 to 1.9 ± 0.10 octaves), and not at all in layer 5/6 (1.8 ± 0.10 to 1.7 ± 0.12 octaves). The results provide an estimate of the laminar and spectral extent of thalamocortical projections and support the hypothesis that intracortical pathways contribute to spectral integration in A1.

Download Full-text

Nicotine Enhances Amplitude and Consistency of Timing of Responses to Acoustic Trains in A1

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.597401 ◽

2021 ◽

Vol 15 ◽

Author(s):

Irakli Intskirveli ◽

Raju Metherate

Keyword(s):

Current Source ◽

Primary Auditory Cortex ◽

Middle Layer ◽

Auditory Brainstem ◽

Auditory Brainstem Responses ◽

Response Dynamics ◽

Layer 4 ◽

Deep Layers ◽

Multiple Trials ◽

40 Hz

Systemic nicotine enhances neural processing in primary auditory cortex (A1) as determined using tone-evoked, current-source density (CSD) measurements. For example, nicotine enhances the characteristic frequency (CF)-evoked current sink in layer 4 of A1, increasing amplitude and decreasing latency. However, since presenting auditory stimuli within a stream of stimuli increases the complexity of response dynamics, we sought to determine the effects of nicotine on CSD responses to trains of CF stimuli (one-second trains at 2–40 Hz; each train repeated 25 times). CSD recordings were obtained using a 16-channel multiprobe inserted in A1 of urethane/xylazine-anesthetized mice, and analysis focused on two current sinks in the middle (layer 4) and deep (layers 5/6) layers. CF trains produced adaptation of the layer 4 response that was weak at 2 Hz, stronger at 5–10 Hz and complete at 20–40 Hz. In contrast, the layer 5/6 current sink exhibited less adaptation at 2–10 Hz, and simultaneously recorded auditory brainstem responses (ABRs) showed no adaptation even at 40 Hz. Systemic nicotine (2.1 mg/kg) enhanced layer 4 responses throughout the one-second stimulus train at rates ≤10 Hz. Nicotine enhanced both response amplitude within each train and the consistency of response timing across 25 trials. Nicotine did not alter the degree of adaptation over one-second trials, but its effect to increase amplitudes revealed a novel, slower form of adaptation that developed over multiple trials. Nicotine did not affect responses that were fully adapted (20–40 Hz trains), nor did nicotine affect any aspect of the layer 5/6 current sink or ABRs. The overall effect of nicotine in layer 4 was to enhance all responses within each train, to emphasize earlier trials across multiple trials, and to improve the consistency of timing across all trials. These effects may improve processing of complex acoustic streams, including speech, that contain information in the 2–10 Hz range.

Download Full-text

Physiology, Pharmacology, and Topography of Cholinergic Neocortical Oscillations In Vitro

Journal of Neurophysiology ◽

10.1152/jn.1997.77.5.2427 ◽

1997 ◽

Vol 77 (5) ◽

pp. 2427-2445 ◽

Cited By ~ 61

Author(s):

Heath S. Lukatch ◽

M. Bruce Maciver

Keyword(s):

Current Source ◽

Brain Slices ◽

Receptor Activation ◽

Brain Regions ◽

Oscillatory Activity ◽

Cortical Layers ◽

Eeg Activity ◽

Layer 2

Lukatch, Heath S. and M. Bruce MacIver. Physiology, pharmacology, and topography of cholinergic neocortical oscillations in vitro. J. Neurophysiol. 77: 2427–2445, 1997. Rat neocortical brain slices generated rhythmic extracellular field [microelectroencephalogram (micro-EEG)] oscillations at theta frequencies (3–12 Hz) when exposed to pharmacological conditions that mimicked endogenous ascending cholinergic and GABAergic inputs. Use of the specific receptor agonist and antagonist carbachol and bicuculline revealed that simultaneous muscarinic receptor activation and γ-aminobutyric acid-A (GABAA)-mediated disinhibition werenecessary to elicit neocortical oscillations. Rhythmic activity was independent of GABAB receptor activation, but required intact glutamatergic transmission, evidenced by blockade or disruption of oscillations by 6-cyano-7-nitroquinoxaline-2,3-dione and (±)-2-amino-5-phosphonovaleric acid, respectively. Multisite mapping studies showed that oscillations were localized to areas 29d and 18b (Oc2MM) and parts of areas 18a and 17. Peak oscillation amplitudes occurred in layer 2/3, and phase reversals were observed in layers 1 and 5. Current source density analysis revealed large-amplitude current sinks and sources in layers 2/3 and 5, respectively. An initial shift in peak inward current density from layer 1 to layer 2/3 indicated that two processes underlie an initial depolarization followed by oscillatory activity. Laminar transections localized oscillation-generating circuitry to superficial cortical layers and sharp-spike-generating circuitry to deep cortical layers. Whole cell recordings identified three distinct cell types based on response properties during rhythmic micro-EEG activity: oscillation-on (theta-on) and -off (theta-off) neurons, and transiently depolarizing glial cells. Theta-on neurons displayed membrane potential oscillations that increased in amplitude with hyperpolarization (from −30 to −90 mV). This, taken together with a glutamate antagonist-induced depression of rhythmic micro-EEG activity, indicated that cholinergically driven neocortical oscillations require excitatory synaptic transmission. We conclude that under the appropriate pharmacological conditions, neocortical brain slices were capable of producing localized theta frequency oscillations. Experiments examining oscillation physiology, pharmacology, and topography demonstrated that neocortical brain slice oscillations share many similarities with the in vivo and in vitro theta EEG activity recorded in other brain regions.

Download Full-text

Optogenetic stimulation of the VTA modulates a frequency-specific gain of thalamocortical inputs in infragranular layers of the auditory cortex

10.1101/669168 ◽

2019 ◽

Cited By ~ 1

Author(s):

Michael G. K. Brunk ◽

Katrina E. Deane ◽

Martin Kisse ◽

Matthias Deliano ◽

Silvia Vieweg ◽

...

Keyword(s):

Auditory Cortex ◽

Information Transfer ◽

Cortical Plasticity ◽

Current Source ◽

Primary Auditory Cortex ◽

Mongolian Gerbils ◽

Spectral Processing ◽

Optogenetic Stimulation ◽

Spectral Integration ◽

Stimulation Of

AbstractBackgroundReward 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. It is currently unknown, however, how the VTA circuitry thereby influences cortical frequency information processing and spectral integration. In this study, we therefore 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.ResultsWhile 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 further persisted over more than 30 minutes after VTA stimulation.ConclusionsAltogether, 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. Our findings thereby demonstrate a cellular and circuit substrate for the influence of reinforcement-evaluating brain systems on sensory processing in the auditory cortex.

Download Full-text

Optogenetic stimulation of the VTA modulates a frequency-specific gain of thalamocortical inputs in infragranular layers of the auditory cortex

Scientific Reports ◽

10.1038/s41598-019-56926-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Michael G. K. Brunk ◽

Katrina E. Deane ◽

Martin Kisse ◽

Matthias Deliano ◽

Silvia Vieweg ◽

...

Keyword(s):

Auditory Cortex ◽

Information Transfer ◽

Cortical Plasticity ◽

Current Source ◽

Primary Auditory Cortex ◽

Mongolian Gerbils ◽

Spectral Processing ◽

Optogenetic Stimulation ◽

Spectral Integration ◽

Stimulation Of

AbstractReward 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.

Download Full-text

Cross-Whisker Adaptation of Neurons in Layer 2/3 of the Rat Barrel Cortex

Frontiers in Systems Neuroscience ◽

10.3389/fnsys.2021.646563 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yonatan Katz ◽

Ilan Lampl

Keyword(s):

Cortical Neurons ◽

Barrel Cortex ◽

Receptive Fields ◽

Repetitive Stimulation ◽

Complex Environments ◽

Cortical Cells ◽

High Responsiveness ◽

Layer 2 ◽

Layer 4 ◽

Stimulation Of

Neurons in the barrel cortex respond preferentially to stimulation of one principal whisker and weakly to several adjacent whiskers. Such integration exists already in layer 4, the pivotal recipient layer of thalamic inputs. Previous studies show that cortical neurons gradually adapt to repeated whisker stimulations and that layer 4 neurons exhibit whisker specific adaptation and no apparent interactions with other whiskers. This study aimed to study the specificity of adaptation of layer 2/3 cortical cells. Towards this aim, we compared the synaptic response of neurons to either repetitive stimulation of one of two responsive whiskers or when repetitive stimulation of the two whiskers was interleaved. We found that in most layer 2/3 cells adaptation is whisker-specific. These findings indicate that despite the multi-whisker receptive fields in the cortex, the adaptation process for each whisker-pathway is mostly independent of other whiskers. A mechanism allowing high responsiveness in complex environments.

Download Full-text

Laminar profile of task-related plasticity in ferret primary auditory cortex

10.1101/354910 ◽

2018 ◽

Author(s):

Nikolas A. Francis ◽

Diego Elgueda ◽

Bernhard Englitz ◽

Jonathan B. Fritz ◽

Shihab A. Shamma

Keyword(s):

Selective Attention ◽

Auditory Cortex ◽

Task Performance ◽

Current Source ◽

Receptive Fields ◽

Primary Auditory Cortex ◽

Neural Representation ◽

Auditory Task ◽

Auditory Target ◽

High Gamma

AbstractRapid task-related plasticity is a neural correlate of selective attention in primary auditory cortex (A1). Top-down feedback from higher-order cortex may drive task-related plasticity in A1, characterized by enhanced neural representation of behaviorally meaningful sounds during auditory task performance. Since intracortical connectivity is greater within A1 layers 2/3 (L2/3) than in layers 4-6 (L4-6), we hypothesized that enhanced representation of behaviorally meaningful sounds might be greater in A1 L2/3 than L4-6. To test this hypothesis and study the laminar profile of task-related plasticity, we trained 2 ferrets to detect pure tones while we recorded laminar activity across a 1.8 mm depth in A1. In each experiment, we analyzed current-source densities (CSDs), high-gamma local field potentials (LFPs), and multi-unit spiking in response to identical acoustic stimuli during both passive listening and active task performance. We found that neural responses to auditory targets were enhanced during task performance, and target enhancement was greater in L2/3 than in L4-6. Spectrotemporal receptive fields (STRFs) computed from CSDs, high-gamma LFPs, and multi-unit spiking showed similar increases in auditory target selectivity, also greatest in L2/3. Our results suggest that activity within intracortical networks plays a key role in shaping the underlying neural mechanisms of selective attention.

Download Full-text

Distinct Manifestations of Cooperative, Multidimensional Stimulus Representations in Different Auditory Forebrain Stations

Cerebral Cortex ◽

10.1093/cercor/bhz299 ◽

2020 ◽

Vol 30 (5) ◽

pp. 3130-3147

Author(s):

Jonathan Y Shih ◽

Kexin Yuan ◽

Craig A Atencio ◽

Christoph E Schreiner

Keyword(s):

Receptive Fields ◽

Medial Geniculate Body ◽

Primary Auditory Cortex ◽

Linear Filter ◽

Auditory Information ◽

Stimulus Response ◽

Spectral Integration ◽

Medial Geniculate ◽

A1 Neurons ◽

Stimulus Features

Abstract Classic spectrotemporal receptive fields (STRFs) for auditory neurons are usually expressed as a single linear filter representing a single encoded stimulus feature. Multifilter STRF models represent the stimulus-response relationship of primary auditory cortex (A1) neurons more accurately because they can capture multiple stimulus features. To determine whether multifilter processing is unique to A1, we compared the utility of single-filter versus multifilter STRF models in the medial geniculate body (MGB), anterior auditory field (AAF), and A1 of ketamine-anesthetized cats. We estimated STRFs using both spike-triggered average (STA) and maximally informative dimension (MID) methods. Comparison of basic filter properties of first maximally informative dimension (MID1) and second maximally informative dimension (MID2) in the 3 stations revealed broader spectral integration of MID2s in MGBv and A1 as opposed to AAF. MID2 peak latency was substantially longer than for STAs and MID1s in all 3 stations. The 2-filter MID model captured more information and yielded better predictions in many neurons from all 3 areas but disproportionately more so in AAF and A1 compared with MGBv. Significantly, information-enhancing cooperation between the 2 MIDs was largely restricted to A1 neurons. This demonstrates significant differences in how these 3 forebrain stations process auditory information, as expressed in effective and synergistic multifilter processing.

Download Full-text