Neurons In Rat Auditory Cortex Research Articles

Using time difference analysis algorithms to measure the response time of rat auditory cortex neurons to auditory nerve stimulation

Measurement of the information flow along the ascending auditory pathway from the periphery to the auditory cortex (AC) has been given much attention in neurocomputation. While the neurophysiological mechanisms of the auditory pathway have been well studied, the temporal resolution and relationships among the auditory centers are still under investigation, especially when suffering from acoustic trauma that results in peripheral deficits and neural signal changes in the auditory system. In this study, we measured rat AC neurons and auditory nerve (AN) signals in digital format by using two new algorithms to calculate the neural response time of the AC neurons to electrical stimulation of the AN and quantify the neural information flow in the temporal domain. One algorithm compared time difference of neural spikes directly, which was based on the conventional idea of spike train in neurocomputation. The other employed a modified cross-correlation algorithm. Both algorithms shared the same pre-signal processing of spike selection. The statistical results by the two methods were compared and various parameters in the algorithms and their impact on the accuracy of the results were discussed. To test the effectiveness of the proposed method, the time difference between the AC to AN activities was calculated by both algorithms with raw neural signals collected. The neural signals from the animals were measured before and after noise trauma, and one of the animals received intra-modiolus electrical stimulation (IMES) to stimulate the AN. The results from using the two algorithms were generally consistent, and the biological mechanisms behind the time delay results between AC and AN activities were discussed.

Nonuniform impacts of forward suppression on neural responses to preferred stimuli and nonpreferred stimuli in the rat auditory cortex.

In natural conditions, human and animals need to extract target sound information from noisy acoustic environments for communication and survival. However, how the contextual environmental sounds impact the tuning of central auditory neurons to target sound source azimuth over a wide range of sound levels is not fully understood. Here, we determined the azimuth-level response areas (ALRAs) of rat auditory cortex neurons by recording their responses to probe tones varying with levels and sound source azimuths under both quiet (probe alone) and forward masking conditions (preceding noise + probe). In quiet, cortical neurons responded stronger to their preferred stimuli than to their nonpreferred stimuli. In forward masking conditions, an effective preceding noise reduced the extents of the ALRAs and suppressed the neural responses across the ALRAs by decreasing the response strength and lengthening the first-spike latency. The forward suppressive effect on neural response strength was increased with increasing masker level and decreased with prolonging the time interval between masker and probe. For a portion of cortical neurons studied, the effects of forward suppression on the response strength to preferred stimuli was weaker than those to nonpreferred stimuli, and the recovery from forward suppression of the response strength to preferred stimuli was earlier than that to nonpreferred stimuli. We suggest that this nonuniform forward suppression of neural responses to preferred stimuli and to nonpreferred stimuli is important for cortical neurons to maintain their relative stable preferences for target sound source azimuth and level in noisy acoustic environments.

The impact of preceding noise on the frequency tuning of rat auditory cortex neurons

BackgroundIn a natural environment, contextual noise frequently occurs with a signal sound for detection or discrimination in a temporal relation. However, the representation of sound frequency by auditory cortical neurons in a noisy environment is not fully understood. Therefore, the purpose of this study was to explore the impact of contextual noise on the cortical tuning to signal sound frequency in order to better understand the mechanism of cortical frequency coding in a complex acoustical environment.ResultsWe compared the excitatory frequency-level receptive fields (FLRFs) of neurons in the rat primary auditory cortex determined under both quiet and preceding noise conditions. Based on the changes of minimum threshold and the extent of FLRF of auditory cortical neurons, we found that the FLRFs of a cortical neuron were modulated dynamically by a varying preceding noise. When the interstimulus interval between noise and the probe tone was constant, the modulation of the FLRF increased as the level of noise was increased. If the preceding noise level was constant, the modulation decreased when the interstimulus interval was increased. Preceding noise sharpened the bandwidth of the FLRFs of 47.6% tested neurons. Moreover, preceding noise shifted the CFs of 47.6% neurons by more than 0.25 octaves, while the CFs of the rest of the neurons remained relatively unchanged.ConclusionsThe results indicate that the cortical representation of sound frequency is dynamically modulated by contextual acoustical environment, and that there are cortical neurons whose characteristic frequencies were resistant to the interference of contextual noise.

Heterosynaptic plasticity induced by intracellular tetanization in layer 2/3 pyramidal neurons in rat auditory cortex

Associative Hebbian-type synaptic plasticity underlies the mechanisms of learning and memory; however, Hebbian learning rules lead to runaway dynamics of synaptic weights and lack mechanisms for synaptic competition.Heterosynaptic plasticity may solve these problems by complementing plasticity at synapses that were active during the induction, with opposite-sign changes at non-activated synapses. In visual cortex, a potential candidate mechanism for normalization is plasticity induced by a purely postsynaptic protocol, intracellular tetanization. Here we asked if intracellular tetanization can induce long-term plasticity in auditory cortex. We recorded excitatory postsynaptic potentials (EPSPs) of regular (n =76) and all-or-none (n =24) type in layer 2/3 pyramidal cells in slices from rat auditory cortex. After intracellular tetanization, 32 of 76 regular inputs (42%) showed long-term depression, 21 inputs (28%) showed potentiation and 23 inputs (30%) did not change. The direction of plasticity correlated with the initial release probability: inputs with initially low release probability tended to be potentiated, while inputs with high release probability tended to be depressed. Thus, intracellular tetanization had a normalizing effect on synaptic efficacy. Induction of plasticity by intracellular tetanization required a rise of intracellular [Ca(2+)], because it was impaired by chelating intracellular calcium with EGTA. The long-term changes induced by intracellular tetanization involved both pre and postsynaptic mechanisms. EPSP amplitude changes were correlated with changes of release indices: paired-pulse ratio and the inverse of the coefficient of variation (CV(-2)). Furthermore at some all-or-none synapses, changes of averaged response amplitude were correlated with a change of the failure rate, without a change of the synaptic potency, measured as averaged amplitude of successful responses. Presynaptic components of plastic changes were abolished in experiments with blockade of NO-synthesis and spread, indicating involvement of NO signalling. These results demonstrate that the ability of purely postsynaptic challenges to induce plasticity is a general property of pyramidal neurons of both auditory and visual cortices.

Contextual modulation of frequency tuning of neurons in the rat auditory cortex

In a natural acoustic environment, sound stimuli often occur in a contextual acoustic stream. The aim of the present study was to determine how the frequency tuning of auditory cortical neurons is affected by an acoustic context. A forward masking paradigm was used to determine the frequency receptive fields of rat auditory cortex neurons under quiet and sequential sound conditions. The frequency receptive fields of a cortical neuron were modulated dynamically by a preceding sound stimulus. At a fixed interstimulus interval (ISI), if the preceding sound level was constant, the receptive fields of most neurons were modulated to the greatest extent when the preceding sound frequency was at or near the characteristic frequency of the neuron; if the preceding sound frequency was constant, the modulation was increased with increasing sound stimulus level. When both the frequency and the level of the preceding sound were fixed, the modulation decreased with increasing interstimulus interval. The results indicate that the frequency tuning of auditory cortical neurons is plastic and dynamically modulated in a reverberant acoustical environment, and the degree of modulation depends on both the frequency tuning of the neuron and the contextual acoustical stream.

Excitatory Local Connections of Superficial Neurons in Rat Auditory Cortex

The mammalian cerebral cortex consists of multiple areas specialized for processing information for many different sensory modalities. Although the basic structure is similar for each cortical area, specialized neural connections likely mediate unique information processing requirements. Relative to primary visual (V1) and somatosensory (S1) cortices, little is known about the intrinsic connectivity of primary auditory cortex (A1). To better understand the flow of information from the thalamus to and through rat A1, we made use of a rapid, high-throughput screening method exploiting laser-induced uncaging of glutamate to construct excitatory input maps of individual neurons. We found that excitatory inputs to layer 2/3 pyramidal neurons were similar to those in V1 and S1; these cells received strong excitation primarily from layers 2-4. Both anatomical and physiological observations, however, indicate that inputs and outputs of layer 4 excitatory neurons in A1 contrast with those in V1 and S1. Layer 2/3 pyramids in A1 have substantial axonal arbors in layer 4, and photostimulation demonstrates that these pyramids can connect to layer 4 excitatory neurons. Furthermore, most or all of these layer 4 excitatory neurons project out of the local cortical circuit. Unlike S1 and V1, where feedback to layer 4 is mediated exclusively by indirect local circuits involving layer 2/3 projections to deep layers and deep feedback to layer 4, layer 4 of A1 integrates thalamic and strong layer 4 recurrent excitatory input with relatively direct feedback from layer 2/3 and provides direct cortical output.

Inhibition of voltage-gated channel currents in rat auditory cortex neurons by salicylate

Salicylate is a medicine for anti-inflammation with a side effect of tinnitus. To understand the mechanisms of tinnitus induced by salicylate, we studied the effects of salicylate on voltage-gated ion channels and action potential firing rates in freshly dissociated rat pyramidal neurons in auditory cortex (AC) using the whole-cell patch technique. We found that salicylate reduced the voltage-gated sodium current ( I Na), the delayed rectifier potassium current ( I K(DR)) and the L-type voltage-gated calcium current ( I Ca,L) in concentration-dependent manner. An amount of 1 mM salicylate shifted the steady-state inactivation curve of I Na negatively by about 5 mV, shifted the steady-state activation and inactivation curve of I K(DR) negatively by approximately 14 mV and 17 mV, respectively, and shifted the steady-state activation curve of I Ca,L negatively by about 10 mV. 1 mM salicylate significantly increased the action potential firing rates, ultimately. From the results, we speculated that through affecting the voltage-gated ion channels in AC, an important position in auditory system, salicylate increased the firing rate of neurons and enhanced neuronal excitability on the one hand, increased the excitatory transmitters release and reduced the inhibitory transmitter release on the other hand, thus finally induced tinnitus.

Receptive field plasticity of neurons in rat auditory cortex

Using conventional electrophysiological technique, we investigated the plasticity of the frequency receptive fields (RF) of auditory cortex (AC) neurons in rats. In the AC, when the frequency difference between conditioning stimulus frequency (CSF) and the best frequency (BF) was in the range of 1-4 kHz, the frequency RF of AC neurons shifted. The smaller the differences between CSF and BF, the higher the probability of the RF shift and the greater the degree of the RF shift. To some extent, the plasticity of RF was dependent on the duration of the session of conditioning stimulus (CS). When the frequency difference between CSF and BF was bigger, the duration of the CS session needed to induce the plasticity was longer. The recovery time course of the frequency RF showed opposite changes after CS cessation. The RF shift could be induced by the frequency that was either higher or lower than the control BF, demonstrating no clear directional preference. The frequency RF of some neurons showed bidirectional shift, and the RF of other neurons showed single directional shift. The results suggest that the frequency RF plasticity of AC neurons could be considered as an ideal model for studying plasticity mechanism. The present study also provides important evidence for further study of learning and memory in auditory system.

Sensitivity to simulated directional sound motion in the rat primary auditory cortex.

Sensitivity to simulated directional sound motion in the rat primary auditory cortex. This paper examines neuron responses in rat primary auditory cortex (AI) during sound stimulation of the two ears designed to simulate sound motion in the horizontal plane. The simulated sound motion was synthesized from mathematical equations that generated dynamic changes in interaural phase, intensity, and Doppler shifts at the two ears. The simulated sounds were based on moving sources in the right frontal horizontal quadrant. Stimuli consisted of three circumferential segments between 0 and 30 degrees, 30 and 60 degrees, and 60 and 90 degrees and four radial segments at 0, 30, 60, and 90 degrees. The constant velocity portion of each segment was 0.84 m long. The circumferential segments and center of the radial segments were calculated to simulate a distance of 2 m from the head. Each segment had two trajectories that simulated motion in both directions, and each trajectory was presented at two velocities. Young adult rats were anesthetized, the left primary auditory cortex was exposed, and microelectrode recordings were obtained from sound responsive cells in AI. All testing took place at a tonal frequency that most closely approximated the best frequency of the unit at a level 20 dB above the tuning curve threshold. The results were presented on polar plots that emphasized the two directions of simulated motion for each segment rather than the location of sound in space. The trajectory exhibiting a "maximum motion response" could be identified from these plots. "Neuron discharge profiles" within these trajectories were used to demonstrate neuron activity for the two motion directions. Cells were identified that clearly responded to simulated uni- or multidirectional sound motion (39%), that were sensitive to sound location only (19%), or that were sound driven but insensitive to our location or sound motion stimuli (42%). The results demonstrated the capacity of neurons in rat auditory cortex to selectively process dynamic stimulus conditions representing simulated motion on the horizontal plane. Our data further show that some cells were responsive to location along the horizontal plane but not sensitive to motion. Cells sensitive to motion, however, also responded best to the moving sound at a particular location within the trajectory. It would seem that the mechanisms underlying sensitivity to sound location as well as direction of motion converge on the same cell.

Effects of noradrenaline on frequency tuning of rat auditory cortex neurons.

The selectivity of rat auditory cortex neurons for pure tone frequency was studied during and after ionophoretic application (5-40 nA) of noradrenaline in urethane-anaesthetized rats. The dominant effect induced by noradrenaline was a significant decrease in spontaneous (93/268 cells) and evoked activity (133/268 cells) which outlasted the application. In the whole population of cells (n = 268) the signal-to-noise ratio, computed using as the signal either the mean evoked response or the response at the best frequency, was unchanged during noradrenaline application. It was significantly increased only for cells showing significantly decreased spontaneous activity, and was significantly decreased for cells showing increased spontaneous activity. Frequency selectivity was significantly increased for the whole population during and after noradrenaline application. It was also significantly increased for cells showing significantly decreased evoked activity, and was significantly decreased for cells showing increased evoked activity. The noradrenaline-induced inhibition was not blocked by propranolol (beta antagonist); it was blocked by prazosin (alpha1 antagonist) and partly mimicked by phenylephrine (alpha1 agonist). GABA, which also inhibited spontaneous and evoked activity, slightly increased the signal-to-noise ratio and significant increased frequency selectivity. However, when noradrenaline was ejected in the presence of bicuculline at doses that were able to block GABAergic inhibition, the inhibitory effects of noradrenaline on spontaneous and evoked activity were still observed. The possible function of noradrenaline-induced inhibitions in sensory cortices is briefly discussed.

Representation of the best frequency and response characteristics of neurons in rat auditory cortex: Junsei Horikawa, Susumu Ito, Yutaka Hosokawa, Tomoo Homma, and Keiichi Murata, Department of Neurophysiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10, Kandasurugadai, Chiyodaku, Tokyo 101, Japan

Representation of the best frequency and response characteristics of neurons in rat auditory cortex: Junsei Horikawa, Susumu Ito, Yutaka Hosokawa, Tomoo Homma, and Keiichi Murata, Department of Neurophysiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10, Kandasurugadai, Chiyodaku, Tokyo 101, Japan