Ryohei Kanzaki

Cortical Mapping of Mismatch Negativity with Deviance Detection Property in Rat

Mismatch Negativity (MMN) is an N-methyl-d-aspartic acid (NMDA)-mediated, negative deflection in human auditory evoked potentials in response to a cognitively discriminable change. MMN-like responses have been extensively investigated in animal models, but the existence of MMN equivalent is still controversial. In this study, we aimed to investigate how closely the putative MMN (MMNp) in rats exhibited the comparable properties of human MMN. We used a surface microelectrode array with a grid of 10×7 recording sites within an area of 4.5×3.0 mm to densely map evoked potentials in the auditory cortex of anesthetized rats under the oddball paradigm. Firstly, like human MMN, deviant stimuli elicited negative deflections in auditory evoked potentials following the positive middle-latency response, termed P1. Secondly, MMNp exhibited deviance-detecting property, which could not be explained by simple stimulus specific adaptation (SSA). Thirdly, this MMNp occurred focally in the auditory cortex, including both the core and belt regions, while P1 activation focus was obtained in the core region, indicating that both P1 and MMNp are generated in the auditory cortex, yet the sources of these signals do not completely overlap. Fourthly, MMNp significantly decreased after the application of AP5 (D-(-)-2-amino-5-phosphonopentanoic acid), an antagonist at NMDA receptors. In stark contrast, AP5 affected neither P1 amplitude nor SSA of P1. These results provide compelling evidence that the MMNp we have examined in rats is functionally comparable to human MMN. The present work will stimulate translational research into MMN, which may help bridge the gap between electroencephalography (EEG)/magnetoencephalography (MEG) studies in humans and electrophysiological studies in animals.

Pre-Attentive, Context-Specific Representation of Fear Memory in the Auditory Cortex of Rat

Neural representation in the auditory cortex is rapidly modulated by both top-down attention and bottom-up stimulus properties, in order to improve perception in a given context. Learning-induced, pre-attentive, map plasticity has been also studied in the anesthetized cortex; however, little attention has been paid to rapid, context-dependent modulation. We hypothesize that context-specific learning leads to pre-attentively modulated, multiplex representation in the auditory cortex. Here, we investigate map plasticity in the auditory cortices of anesthetized rats conditioned in a context-dependent manner, such that a conditioned stimulus (CS) of a 20-kHz tone and an unconditioned stimulus (US) of a mild electrical shock were associated only under a noisy auditory context, but not in silence. After the conditioning, although no distinct plasticity was found in the tonotopic map, tone-evoked responses were more noise-resistive than pre-conditioning. Yet, the conditioned group showed a reduced spread of activation to each tone with noise, but not with silence, associated with a sharpening of frequency tuning. The encoding accuracy index of neurons showed that conditioning deteriorated the accuracy of tone-frequency representations in noisy condition at off-CS regions, but not at CS regions, suggesting that arbitrary tones around the frequency of the CS were more likely perceived as the CS in a specific context, where CS was associated with US. These results together demonstrate that learning-induced plasticity in the auditory cortex occurs in a context-dependent manner.

Stimulus Phase Locking of Cortical Oscillation for Auditory Stream Segregation in Rats

The phase of cortical oscillations contains rich information and is valuable for encoding sound stimuli. Here we hypothesized that oscillatory phase modulation, instead of amplitude modulation, is a neural correlate of auditory streaming. Our behavioral evaluation provided compelling evidences for the first time that rats are able to organize auditory stream. Local field potentials (LFPs) were investigated in the cortical layer IV or deeper in the primary auditory cortex of anesthetized rats. In response to ABA- sequences with different inter-tone intervals and frequency differences, neurometric functions were characterized with phase locking as well as the band-specific amplitude evoked by test tones. Our results demonstrated that under large frequency differences and short inter-tone intervals, the neurometric function based on stimulus phase locking in higher frequency bands, particularly the gamma band, could better describe van Noorden’s perceptual boundary than the LFP amplitude. Furthermore, the gamma-band neurometric function showed a build-up-like effect within around 3 seconds from sequence onset. These findings suggest that phase locking and amplitude have different roles in neural computation, and support our hypothesis that temporal modulation of cortical oscillations should be considered to be neurophysiological mechanisms of auditory streaming, in addition to forward suppression, tonotopic separation, and multi-second adaptation.

Amplitude and phase-locking adaptation of neural oscillation in the rat auditory cortex in response to tone sequence

Sensory adaptation allows stimulus sensitivity to be dynamically modulated according to stimulus statistics and plays pivotal roles in efficient neural computation. Here, it is hypothesized that in the auditory cortex, phase locking of local field potentials (LFPs) to test tones exhibits an adaptation property, i.e., phase-locking adaptation, which is distinct from the amplitude adaptation of oscillatory components. Series of alternating tone sequences were applied in which the inter-tone interval (ITI) and frequency difference (ΔF) between successive tones were varied. Then, adaptation was characterized by the temporal evolution of the band-specific amplitude and phase locking evoked by the test tones. Differences as well as similarities were revealed between amplitude and phase-locking adaptations. First, both amplitude and phase-locking adaptations were enhanced by short ITIs and small ΔFs. Second, the amplitude adaptation was more effective in a higher frequency band, while the phase-locking adaptation was more effective in a lower frequency band. Third, as with the adaptation of multiunit activities (MUAs), the amplitude adaptation occurred mainly within a second, while the phase-locking showed multi-second adaptation specifically in the gamma band for short ITI and small ΔF conditions. Fourth, the amplitude adaptation and phase-locking adaptation were co-modulated in a within-second time scale, while this co-modulation was not observed in a multi-second time scale. These findings suggest that the amplitude and phase-locking adaptations have different mechanisms and functions. The phase-locking adaptation is likely to play more crucial roles in encoding a temporal structure of stimulus than the amplitude adaptation.

Learning-Stage-Dependent Plasticity of Temporal Coherence in the Auditory Cortex of Rats

Temporal coherence among neural populations may contribute importantly to signal encoding, specifically by providing an optimal tradeoff between encoding reliability and efficiency. Here, we considered the possibility that learning modulates the temporal coherence among neural populations in association with well-characterized map plasticity. We previously demonstrated that, in appetitive operant conditioning tasks, the tone-responsive area globally expanded during the early stage of learning, but shrank during the late stage. The present study further showed that phase locking of the first spike to band-specific oscillations of local field potentials (LFPs) significantly increased during the early stage of learning but decreased during the late stage, suggesting that neurons in A1 were more synchronously activated during early learning, whereas they were more asynchronously activated once learning was completed. Furthermore, LFP amplitudes increased during early learning but decreased during later learning. These results suggest that, compared to naïve encoding, early-stage encoding is more reliable but energy-consumptive, whereas late-stage encoding is more energetically efficient. Such a learning-stage-dependent encoding strategy may underlie learning-induced, non-monotonic map plasticity. Accumulating evidence indicates that the cholinergic system is likely to be a shared neural substrate of the processes for perceptual learning and attention, both of which modulate neural encoding in an adaptive manner. Thus, a better understanding of the links between map plasticity and modulation of temporal coherence will likely lead to a more integrated view of learning and attention.

Decoding of the sound frequency from the steady-state neural activities in rat auditory cortex

In the auditory cortex, onset activities have been extensively investigated as a cortical representation of sound information such as sound frequency. Yet, less attention has been paid to date to steady-state activities following the onset activities. In this study, we used machine learning to investigate whether steady-state activities in the presence of continuous sounds represent the sound frequency. Sparse Logistic Regression (SLR) decoded the sound frequency from band specific power or phase locking value (PLV) of local field potentials (LFP) from the fourth layer of the auditory cortex of anesthetized rats. Consequently, we found that SLR was able to decode the sound frequency from steady-state neural activities as well as onset activities. This result demonstrates that the steady-state activities contain information about the sound such as sound frequency.

Population activity in auditory cortex of the awake rat revealed by recording with dense microelectrode array

Cortical mechanisms of auditory perception include temporal interaction between neuronal ensembles in a functional cortical structure such as a place code of frequency, or tonotopic map. To investigate the mechanism, a recording method is needed to densely map spatio-temporal activity pattern within the predefined tonotopic organization specifically in the awake condition. The present study has proposed and developed an experimental system that is capable of simultaneous neural recording with a grid array of 100 sites with 400-μm inter-electrode distance in the 4th layer of auditory cortex of awake rat. Both multiunit activities (MUA) and local field potentials (LFPs) confirmed the tonotopic map in the auditory cortex. In addition, spectral powers in higher frequency components (4-120 Hz) were enhanced and a lower frequency component (1-4 Hz) was reduced during waking. Phase synchronization between recording sites in the gamma-band oscillatory activity was generally smaller in the awake cortex than in the anesthetized cortex. These results have proven the feasibility of our recording and will open a new avenue to investigate neural activities in the functional map of awake cortex.