scholarly journals Nicotinic neuromodulation in auditory cortex requires MAPK activation in thalamocortical and intracortical circuits

2012 ◽  
Vol 107 (10) ◽  
pp. 2782-2793 ◽  
Author(s):  
Irakli Intskirveli ◽  
Raju Metherate
Keyword(s):  
Auditory Cortex ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Current Source ◽  
Primary Auditory Cortex ◽  
Mek Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Evoked Responses ◽  
Intracortical Circuits ◽  
Sensory Evoked

Activation of nicotinic acetylcholine receptors (nAChRs) by systemic nicotine enhances sensory-cognitive function and sensory-evoked cortical responses. Although nAChRs mediate fast neurotransmission at many synapses in the nervous system, nicotinic regulation of cortical processing is neuromodulatory. To explore potential mechanisms of nicotinic neuromodulation, we examined whether intracellular signal transduction involving mitogen-activated protein kinase (MAPK) contributes to regulation of tone-evoked responses in primary auditory cortex (A1) in the mouse. Systemic nicotine enhanced characteristic frequency (CF) tone-evoked current-source density (CSD) profiles in A1, including the shortest-latency (presumed thalamocortical) current sink in layer 4 and longer-latency (presumed intracortical) sinks in layers 2–4, by increasing response amplitudes and decreasing response latencies. Microinjection of the MAPK kinase (MEK) inhibitor U0126 into the thalamus, targeting the auditory thalamocortical pathway, blocked the effect of nicotine on the initial (thalamocortical) CSD component but did not block enhancement of longer-latency (intracortical) responses. Conversely, microinjection of U0126 into supragranular layers of A1 blocked nicotine's effect on intracortical, but not thalamocortical, CSD components. Simultaneously with enhancement of CF-evoked responses, responses to spectrally distant (nonCF) stimuli were reduced, implying nicotinic “sharpening” of frequency receptive fields, an effect also blocked by MEK inhibition. Consistent with these physiological results, acoustic stimulation with nicotine produced immunolabel for activated MAPK in A1, primarily in layer 2/3 cell bodies. Immunolabel was blocked by intracortical microinjection of the nAChR antagonist dihydro-β-erythroidine, but not methyllycaconitine, implicating α4β2*, but not α7, nAChRs. Thus activation of MAPK in functionally distinct forebrain circuits—thalamocortical, local intracortical, and long-range intracortical—underlies nicotinic neuromodulation of A1.

Intracortical Circuits in Rat Anterior Cingulate Cortex Are Activated by Nociceptive Inputs Mediated by Medial Thalamus

2006 ◽  
Vol 96 (6) ◽  
pp. 3409-3422 ◽  
Author(s):  
Jenq-Wei Yang ◽  
Hsi-Chien Shih ◽  
Bai-Chuang Shyu
Keyword(s):  
Anterior Cingulate Cortex ◽  
Current Source ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
High Frequency Stimulation ◽  
Evoked Responses ◽  
Synaptic Organization ◽  
Sprague Dawley ◽  
Intracortical Circuits ◽  
Layer V

We investigated the afferents and intracortical synaptic organization of the anterior cingulate cortex (ACC) during noxious electrical stimulation. Extracellular field potentials were recorded simultaneously from 16 electrodes spanning all layers of the ACC in male Sprague–Dawley rats anesthetized by halothane inhalation. Laminar-specific transmembrane currents were calculated with the current source density analysis method. Two major groups of evoked sink currents were identified: an early group (latency = 54.04 ± 2.12 ms; 0.63 ± 0.07 mV/mm2) in layers V–VI and a more intense late group (latency = 80.07 ± 4.85 ms; 2.16 ± 0.22 mV/mm2) in layer II/III and layer V. Multiunit activities were evoked mainly in layer V and deep layer II/III with latencies similar to that of the early and late sink groups. The evoked EPSP latencies of pyramidal neurons in layers II/III and V related closely with the sink currents. The sink currents were inhibited by intracortical injection of CNQX (1 mM, 1 μl), a glutaminergic receptor antagonist, and enhanced by intraperitoneal (5 mg/kg) and intracortical (10 μg/μl, 1 μl) injection of morphine, a μ-opioid receptor agonist. Paired-pulse depression was observed with interpulse intervals of 50 to 1,000 ms. High-frequency stimulation (100 Hz, 11 pulses) enhanced evoked responses in the ACC and evoked medial thalamic (MT) unit activities. MT lesions blocked evoked responses in the ACC. Our results demonstrated that two distinct synaptic circuits in the ACC were activated by noxious stimuli and that the MT is the major thalamic relay that transmits nociceptive information to the ACC.

Activation of Spinal Wide Dynamic Range Neurons by Intracutaneous Microinjection of Nicotine

1999 ◽  
Vol 82 (6) ◽  
pp. 3046-3055 ◽  
Author(s):  
Steven L. Jinks ◽  
E. Carstens
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Threshold Region ◽  
Partial Recovery ◽  
Evoked Responses ◽  
Wide Dynamic Range ◽  
Analgesic Effects ◽  
Wdr Neurons

Nicotine evokes pain in the skin and oral mucosa and excites a subpopulation of cutaneous nociceptors, but little is known about the central transmission of chemogenic pain. We have investigated the responses of lumbar spinal wide dynamic range (WDR)-type dorsal horn neurons to intracutaneous (ic) microinjection of nicotine in pentobarbital-anesthetized rats. Nearly all (97%) units responded to nicotine microinjected ic (1 μl) into the low-threshold region of the hind-paw mechanosensitive receptive field in a concentration-related manner (0.01–10%). Responses to repeated injections of 10% nicotine exhibited tachyphylaxis at 5-, 10-, and 15-min interstimulus intervals. Significant tachyphylaxis was not seen with 1% nicotine. All nicotine-responsive units tested ( n = 30) also responded to ic histamine (1 μl, 3%) and did not exhibit tachyphylaxis to repeated histamine. However, there was significant cross-tachyphylaxis of nicotine to histamine. Thus 5 min after ic nicotine, histamine-evoked responses were attenuated significantly compared with the initial histamine-evoked response prior to nicotine, with partial recovery over the ensuing 15 min. Neuronal excitation by ic nicotine was not mediated by histamine H1 receptors because ic injection of the H1 receptor antagonist, cetirizine, had no effect on ic nicotine-evoked responses, whereas it significantly attenuated ic histamine-evoked responses in the same neurons. The lowest-threshold portion of cutaneous receptive fields showed a significant expansion in area at 20 min after ic nicotine 10%, indicative of sensitization. Responses to 1% nicotine were significantly reduced after ic injection of the nicotinic antagonist, mecamylamine (0.1% ic), with no recovery over the ensuing 40–60 min. These data indicate that nicotine ic excites spinal WDR neurons, partly via neuronal nicotinic acetylcholine receptors that are presumably expressed in cutaneous nociceptor terminals. Repeated injections of high concentrations of nicotine led to tachyphylaxis and cross-tachyphylaxis with histamine, possibly relevant to peripheral analgesic effects of nicotine.

Current Source Density Profiles of Stimulus-Specific Adaptation in Rat Auditory Cortex

2009 ◽  
Vol 102 (3) ◽  
pp. 1483-1490 ◽  
Author(s):  
Francois D. Szymanski ◽  
Jose A. Garcia-Lazaro ◽  
Jan W. H. Schnupp
Keyword(s):  
Auditory Cortex ◽  
Current Source ◽  
Primary Auditory Cortex ◽  
Auditory Pathway ◽  
Afferent Input ◽  
Current Source Density ◽  
Specific Adaptation ◽  
Source Density ◽  
Density Analysis ◽  
Layer V

Neurons in primary auditory cortex (A1) are known to exhibit a phenomenon known as stimulus-specific adaptation (SSA), which means that, when tested with pure tones, they will respond more strongly to a particular frequency if it is presented as a rare, unexpected “oddball” stimulus than when the same stimulus forms part of a series of common, “standard” stimuli. Although SSA has occasionally been observed in midbrain neurons that form part of the paraleminscal auditory pathway, it is thought to be weak, rare, or nonexistent among neurons of the leminscal pathway that provide the main afferent input to A1, so that SSA seen in A1 is likely generated within A1 by local mechanisms. To study the contributions that neural processing within the different cytoarchitectonic layers of A1 may make to SSA, we recorded local field potentials in A1 of the rat in response to standard and oddball tones and subjected these to current source density analysis. Although our results show that SSA can be observed throughout all layers of A1, right from the earliest part of the response, there are nevertheless significant differences between layers, with SSA becoming significantly stronger as stimulus-related activity passes from the main thalamorecipient layers III and IV to layer V.

Rabbit retinal ganglion cell responses mediated by α-bungarotoxin-sensitive nicotinic acetylcholine receptors

2002 ◽  
Vol 19 (4) ◽  
pp. 427-438 ◽  
Author(s):  
B.T. REED ◽  
F.R. AMTHOR ◽  
K.T. KEYSER
Keyword(s):  
Ganglion Cell ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Ganglion Cells ◽  
Cell Types ◽  
Evoked Responses ◽  
Retinal Ganglion ◽  
Nicotinic Acetylcholine ◽  
Low Concentrations ◽  
Cholinergic Agents

The responses of many ganglion cells in the rabbit retina are mediated, at least in part, by acetylcholine (ACh) acting on neuronal nicotinic acetylcholine receptors (nAChRs). nAChRs are comprised of α and β subunits; three β subunits and nine α subunits of nAChRs have been identified and these subunits can combine to form a large number of functionally distinct nAChR subtypes. We examined the effects of cholinergic agents on the light-evoked responses of ganglion cells to determine which nAChR subtypes mediate the effects of ACh. Extracellular recordings of retinal ganglion cells were made in intact everted eyecup preparations and nicotinic agonists and antagonists were added to the superfusate. While several ganglion cell classes exhibited methyllycaconitine (MLA) sensitivity, the directionally selective (DS) ganglion cells were most sensitive; exposure to 30 nanomolar MLA, a concentration reportedly too low to affect αBgt-insensitive nAChRs, suppressed the stimulus-evoked responses of DS cells without eliminating directional selectivity. Epibatidine, which at low concentrations is an agonist selective for αBgt-insensitive nAChRs, stimulated firing of various cell types including DS ganglion cells at low nanomolar concentrations. The effects of the various agents tested persisted under cobalt-induced synaptic blockade. The low nanomolar MLA and epibatidine sensitivity of DS cells suggests that DS ganglion cells express both αBgt-sensitive and αBgt-insensitive nAChRs. Other ganglion cell types appear to express only αBgt-sensitive nAChRs but not αBgt-insensitive nAChRs.

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

2019 ◽  
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.

scholarly journals Layer-Specific Intracortical Amplification Shortens the Lifetime of Thalamocortical Repetition Suppression in Auditory Cortex

2021 ◽  
Author(s):  
Jing Ma ◽  
Michael Brunk ◽  
Artur Matysiak ◽  
Nina Härtwich ◽  
Frank Ohl ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Current Source ◽  
Primary Auditory Cortex ◽  
Meriones Unguiculatus ◽  
Neural Adaptation ◽  
Fundamental Aspect ◽  
Mongolian Gerbils ◽  
Cortical Layers ◽  
Repetition Suppression ◽  
Granular Layers

Abstract Neural adaptation in sensory cortex serves important sensory functions, and is altered by various neurophsychiatric diseases. Although adaptation is a widely studied phenomenon, much remains unknown about its underlying mechanisms on a cortical circuit level. Here, we investigated repetition suppression as fundamental aspect of adaptation by layer-specific current source density analyses of synaptic mass activities in primary auditory cortex of anesthetized Mongolian gerbils (Meriones unguiculatus). We disentangled different synaptic contributions to repetition suppression in different cortical layers, and separated thalamocortical from intracortical inputs by cortical silencing with GABAA-agonist muscimol. We systematically varied stimulus onset intervals and employed statistically robust model fitting based on bootstrapping to determine the full suppression kinetics of different synaptic responses in the steady state. Whereas thalamocortical input to granular and infragranular layers was governed by longer lasting repetition suppression, most likely reflecting depression of thalamocortical synapses, intracortical amplification in granular layers shortened the lifetime of suppression by re-enhancing granular responses mainly through synchronization of synaptic events. With increasing latency, the shorter lasting suppression kinetics observed in granular layers at early latencies (<100ms) passed on to deeper layers replacing the longer lasting infragranular suppression kinetics. Granular circuit dynamics can therefore actively shape neural adaptation across cortical layers.

scholarly journals Spectral Resolution of Monkey Primary Auditory Cortex (A1) Revealed With Two-Noise Masking

2006 ◽  
Vol 96 (3) ◽  
pp. 1105-1115 ◽  
Author(s):  
Yonatan I. Fishman ◽  
Mitchell Steinschneider
Keyword(s):  
Auditory Cortex ◽  
Spectral Resolution ◽  
Goodness Of Fit ◽  
Auditory Evoked Potentials ◽  
Current Source ◽  
Primary Auditory Cortex ◽  
Frequency Separation ◽  
Frequency Resolution ◽  
Noise Masking ◽  
Neural Populations

An important function of the auditory nervous system is to analyze the frequency content of environmental sounds. The neural structures involved in determining psychophysical frequency resolution remain unclear. Using a two-noise masking paradigm, the present study investigates the spectral resolution of neural populations in primary auditory cortex (A1) of awake macaques and the degree to which it matches psychophysical frequency resolution. Neural ensemble responses (auditory evoked potentials, multiunit activity, and current source density) evoked by a pulsed 60-dB SPL pure-tone signal fixed at the best frequency (BF) of the recorded neural populations were examined as a function of the frequency separation (ΔF) between the tone and two symmetrically flanking continuous 80-dB SPL, 50-Hz-wide bands of noise. ΔFs ranged from 0 to 50% of the BF, encompassing the range typically examined in psychoacoustic experiments. Responses to the signal were minimal for ΔF = 0% and progressively increased with ΔF, reaching a maximum at ΔF = 50%. Rounded exponential functions, used to model auditory filter shapes in psychoacoustic studies of frequency resolution, provided excellent fits to neural masking functions. Goodness-of-fit was greatest for response components in lamina 4 and lower lamina 3 and least for components recorded in more superficial cortical laminae. Physiological equivalent rectangular bandwidths (ERBs) increased with BF, measuring nearly 15% of the BF. These findings parallel results of psychoacoustic studies in both monkeys and humans, and thus indicate that a representation of perceptual frequency resolution is available at the level of A1.

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