Acetylcholine modifies neuronal acoustic rate-level functions in guinea pig auditory cortex by an action at muscarinic receptors

ABSTRACT Cholinergic modification of neuronal responsiveness in auditory cortex includes alteration of spontaneous and tone-evoked neuronal discharge. Previously it was suggested that the effects of acetylcholine (ACh) and muscarinic agonists on neuronal discharge resembled those due to increases in the intensity of acoustic stimuli Acet lcholine (ACh) modifies spontaneous and Often the effects of ACh result in systematic modification of the receptive field of the neuron (for recent reviews, see Ashe and Weinberger, 1990; Weinberger et evoke B discharge of neurons in sensory koniocortex. consist of a change in of responses to different frequencies of acoustic stimuli bethods of recordin single unit dischar e, acoustic logical agents used were similar to those previously reporte

Null Mutations in EphB Receptors Decrease Sharpness of Frequency Tuning in Primary Auditory Cortex

Primary auditory cortex (A1) exhibits a tonotopic representation of characteristic frequency (CF). The receptive field properties of A1 neurons emerge from a combination of thalamic inputs and intracortical connections. However, the mechanisms that guide growth of these inputs during development and shape receptive field properties remain largely unknown. We previously showed that Eph family proteins help establish tonotopy in the auditory brainstem. Moreover, other studies have shown that these proteins shape topography in visual and somatosensory cortices. Here, we examined the contribution of Eph proteins to cortical organization of CF, response thresholds and sharpness of frequency tuning. We examined mice with null mutations in EphB2 and EphB3, as these mice show significant changes in auditory brainstem connectivity. We mapped A1 using local field potential recordings in adult EphB2−/−;EphB3−/− and EphB3−/− mice, and in a central A1 location inserted a 16-channel probe to measure tone-evoked current-source density (CSD) profiles. Based on the shortest-latency current sink in the middle layers, which reflects putative thalamocortical input, we determined frequency receptive fields and sharpness of tuning (Q20) for each recording site. While both mutant mouse lines demonstrated increasing CF values from posterior to anterior A1 similar to wild type mice, we found that the double mutant mice had significantly lower Q20 values than either EphB3−/− mice or wild type mice, indicating broader tuning. In addition, we found that the double mutants had significantly higher CF thresholds and longer onset latency at threshold than mice with wild type EphB2. These results demonstrate that EphB receptors influence auditory cortical responses, and suggest that EphB signaling has multiple functions in auditory system development

Transient and prolonged effects of acetylcholine administered iontophoretically to neurons in cat primary somatosensory cortex

This thesis describes the modulatory effects of acetylcholine (ACh) on neuronal responsiveness in the primary somatosensory cortex of cats. In 52 anesthetized animals, the responses of 440 cells were studied in three series of experiments. In series 1, iontophoretic administration of various doses (7-200 nA) of ACh produced increased firing rates in 16% (33/203) of the neurons tested. Responses to somatic stimuli were modulated by ACh in 29% of the cases. These modulatory effects were predominantly excitatory, with only 5% of the cells being depressed by ACh. In series 2 and 3, 50 nA of ACh applied in the absence of other overt stimula altered the responsiveness of a cell to subsequent tactile stimulation or iontophoretically-applied glutamate. This occurred in 21% (13/61) of the cells. In contrast, when 50 nA of ACh was administered simultaneously with glutamate and/or receptive field stimulation, altered responsiveness occurred in 77% (76/99) of the cases. One-third (32/99) of these cells displayed prolonged changes in responsiveness, lasting from 7 min to over 1 h.Cells modulated by ACh were found in all cortical layers. The percentage of cholinoceptive cells was highest in layer VI (78%), and was not less than 50% in any layer. Both long and short-term potentiating effects of ACh on responses to somatic stimulation and responses to glutamate administration could be reversibly blocked by low iontophoretic doses of atropine

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

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

Enhanced Sensory–Cognitive Processing by Activation of Nicotinic Acetylcholine Receptors

Activation of nicotinic acetylcholine receptors (nAChRs) enhances sensory-cognitive function in human subjects and animal models, yet the neural mechanisms are not fully understood. This review summarizes recent studies on nicotinic regulation of neural processing in the cerebral cortex that point to potential mechanisms underlying enhanced cognitive function. Studies from our laboratory focus on nicotinic regulation of auditory cortex and implications for auditory-cognitive processing, but relevant emerging insights from multiple brain regions are discussed. Although the major contributions of the predominant nAChRs containing α7 (homomeric receptors) or α4 and β2 (heteromeric) subunits are well recognized, recent results point to additional, potentially critical contributions from α2 subunits that are relatively sparse in cortex. Ongoing studies aim to elucidate the specific contributions to cognitive and cortical function of diverse nAChRs. IMPLICATIONS:This review highlights the therapeutic potential of activating nAChRs in the cerebral cortex to enhance cognitive function. Future work also must determine the contributions of relatively rare but important nAChR subtypes, potentially to develop more selective treatments for cognitive deficits

Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions.

Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit- and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral "notch" of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing