Thalamocortical Innervation Pattern in Mouse Auditory and Visual Cortex: Laminar and Cell-Type Specificity.

Despite many previous studies, the functional innervation pattern of thalamic axons and their target specificity remains to be investigated thoroughly. Here, in primary auditory cortical slices, we examined thalamic innervation patterns for excitatory and different types of inhibitory neurons across laminae, by optogenetically stimulating axons from the medial geniculate body. We found that excitatory cells and parvalbumin (PV)-expressing inhibitory neurons across layer 2/3 (L2/3) to L6 are directly innervated by thalamic projections, with the strongest innervation occurring in L4. The innervation of PV neurons is stronger than that of excitatory neurons in the same layer, with a relatively constant ratio between their innervation strengths across layers. For somatostatin and vasoactive intestinal peptide inhibitory neurons, essentially only L4 neurons were innervated by thalamic axons and the innervation was much weaker compared with excitatory and PV cells. In addition, more than half of inhibitory neurons in L1 were innervated, relatively strongly, by thalamic axons. Similar innervation patterns were also observed in the primary visual cortex. Thus, thalamic information can be processed independently and differentially by different cortical layers, in addition to the generally thought hierarchical processing starting from L4. This parallel processing is likely shaped by feedforward inhibition from PV neurons in each individual lamina, and may extend the computation power of sensory cortices.

Interdependent effects of sound duration and amplitude on neuronal onset response in mice inferior colliculus.

In this study, we adopted iso-frequency pure tone bursts to investigate the interdependent effects of sound amplitude/intensity and duration on mice inferior colliculus (IC) neuronal onset responses. On the majority of the sampled neurons (n=57, 89.1%), sound amplitude and duration had effects on the neuronal response to each other by showing complex changes of the rat-intensity function/duration selectivity types and/or best amplitudes (BAs)/durations (BDs), evaluated by spike counts. These results suggested that the balance between the excitatory and inhibitory inputs set by one acoustic parameter, amplitude or duration, affected the neuronal spike counts responses to the other. Neuronal duration selectivity types were altered easily by the low-amplitude sounds while the changes of rate-intensity function types had no obvious preferred stimulus durations. However, the first spike latencies (FSLs) of the onset response neurons were relative stable to iso-amplitude sound durations and changing systematically along with the sound levels. The superimposition of FSL and duration threshold (DT) as a function of stimulus amplitude after normalization indicated that the effects of the sound levels on FSLs are considered on DT actually.

Interaural level difference-dependent gain control and synaptic scaling underlying binaural computation.

Binaural integration in the central nucleus of inferior colliculus (ICC) plays a critical role in sound localization. However, its arithmetic nature and underlying synaptic mechanisms remain unclear. Here, we showed in mouse ICC neurons that the contralateral dominance is created by a "push-pull"-like mechanism, with contralaterally dominant excitation and more bilaterally balanced inhibition. Importantly, binaural spiking response is generated apparently from an ipsilaterally mediated scaling of contralateral response, leaving frequency tuning unchanged. This scaling effect is attributed to a divisive attenuation of contralaterally evoked synaptic excitation onto ICC neurons with their inhibition largely unaffected. Thus, a gain control mediates the linear transformation from monaural to binaural spike responses. The gain value is modulated by interaural level difference (ILD) primarily through scaling excitation to different levels. The ILD-dependent synaptic scaling and gain adjustment allow ICC neurons to dynamically encode interaural sound localization cues while maintaining an invariant representation of other independent sound attributes.

[Digital signal processing of a novel neuron discharge model stimulation strategy for cochlear implants].

OBJECTIVE: To apply the classic leakage integrate-and-fire models, based on the mechanism of the generation of physiological auditory stimulation, in the information processing coding of cochlear implants to improve the auditory result. METHODS: The results of algorithm simulation in digital signal processor (DSP) were imported into Matlab for a comparative analysis. RESULTS: Compared with CIS coding, the algorithm of membrane potential integrate-and-fire (MPIF) allowed more natural pulse discharge in a pseudo-random manner to better fit the physiological structures. CONCLUSION: The MPIF algorithm can effectively solve the problem of the dynamic structure of the delivered auditory information sequence issued in the auditory center and allowed integration of the stimulating pulses and time coding to ensure the coherence and relevance of the stimulating pulse time.

Generation of spike latency tuning by thalamocortical circuits in auditory cortex.

In many sensory systems, the latency of spike responses of individual neurons is found to be tuned for stimulus features and proposed to be used as a coding strategy. Whether the spike latency tuning is simply relayed along sensory ascending pathways or generated by local circuits remains unclear. Here, in vivo whole-cell recordings from rat auditory cortical neurons in layer 4 revealed that the onset latency of their aggregate thalamic input exhibited nearly flat tuning for sound frequency, whereas their spike latency tuning was much sharper with a broadly expanded dynamic range. This suggests that the spike latency tuning is not simply inherited from the thalamus, but can be largely reconstructed by local circuits in the cortex. Dissecting of thalamocortical circuits and neural modeling further revealed that broadly tuned intracortical inhibition prolongs the integration time for spike generation preferentially at off-optimal frequencies, while sharply tuned intracortical excitation shortens it selectively at the optimal frequency. Such push and pull mechanisms mediated likely by feedforward excitatory and inhibitory inputs respectively greatly sharpen the spike latency tuning and expand its dynamic range. The modulation of integration time by thalamocortical-like circuits may represent an efficient strategy for converting information spatially coded in synaptic strength to temporal representation.

Case-control study on the association between qi-stagnation and insomnia.

OBJECTIVE: To investigate the relationship between insomnia and qi-stagnation by using the international standardized measurement of sleep quality and the Traditional Chinese Medicine (TCM) Constitution Scales. METHODS: A survey by means of the TCM Constitution Scales, the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and the Deep Sleep Scale (DSS) in 169 participants aged between 16 and 80 years old was conducted. Comparison was made to examine the sleep quality and insomnia symptoms in the qi-stagnation group and other-constitution group. RESULTS: Univariate analysis found that the qi-stagnation group had a significantly increased risk of difficulty in falling asleep (OR=3.012, and 95% CI 1.310 to 6.923 for PSQI; OR=3.016, and 95% CI 1.358 to 6.709 for DSS) and early waking (OR=3.545, and 95% CI 1.229 to 10.232 for PSQI; OR=2.742, and 95% CI 1.072 to 7.014 for DSS), while the other-constitution group had a significant risk of dreaminess (OR=2.419, and 95% CI 1.154 to 5.072 for PSQI; OR=2.561, and 95% CI 1.116 to 5.880 for DSS). A dose-effect relationship existed between insomnia symptoms and qi-stagnation. Qi-stagnation significantly increased the risk of difficulty in falling asleep and early waking. CONCLUSION: This case-control study revealed that there is a statistically significant association between qi-stagnation and insomnia. Based on this study, we recommend that further research should be conducted for the rehabilitative care and cure of insomnia from the perspective of TCM constitution.

Preceding inhibition silences layer 6 neurons in auditory cortex.

A canonical feedforward circuit is proposed to underlie sensory cortical responses with balanced excitation and inhibition in layer 4 (L4). However, in another input layer, L6, sensory responses and the underlying synaptic circuits remain largely unclear. Here, cell-attached recordings in rat primary auditory cortex revealed that for the majority of L6 excitatory neurons, tonal stimuli did not drive spike responses, but suppressed spontaneous firings. Whole-cell recordings further revealed that the silencing resulted from tone-evoked strong inhibition arriving earlier than excitation. This pattern of inputs can be attributed to a parallel feedforward circuit with both excitatory and inhibitory inputs disynaptically relayed. In contrast, in the other neurons directly driven by thalamic input, stimuli evoked excitation preceding relatively weak inhibition, resulting in robust spike responses. Thus, the dichotomy of L6 response properties arises from two distinct patterns of excitatory-inhibitory interplay. The parallel circuit module generating preceding inhibition may provide a gating mechanism for conditional corticothalamic feedback.

Asymmetry in corticofugal modulation of frequency-tuning in mustached bat auditory system.

Focal electric stimulation of the auditory cortex is well suited for exploration of the function of the corticofugal (descending) system and the neural mechanism of plasticity in the central auditory system, because it evokes changes in frequency-tuning, called best frequency (BF) shifts, as does auditory fear conditioning. The Doppler-shifted constant frequency (DSCF) area of the primary auditory cortex of the mustached bat is highly specialized for fine frequency analysis. Focal electric stimulation of the DSCF area evokes the BF shifts of ipsilateral cortical and collicular neurons away from the BF of stimulated neurons, whereas the stimulation evokes the BF shifts of contralateral cortical and collicular neurons either toward or away from the stimulated BF. The direction of contralateral BF shifts shows a flip-flop, depending on the spatial relationship between the stimulated and recorded neurons. This asymmetry in corticofugal modulation is mostly, if not totally, created by two subdivisions of the stimulated DSCF area that transmit signals to the contralateral DSCF area, presumably through the corpus callosum. This intriguing asymmetry in corticofugal modulation presumably functions for equalization of the reorganization of the frequency maps of the DSCF areas and subcortical auditory nuclei on both sides.

Neuroprotective effects of Buyang Huanwu Decoction on neuronal injury in hippocampus after transient forebrain ischemia in rats.

Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine, has been developed as a drug to be used for treatment of stroke for hundreds of years. However, the underlying mechanisms remain unknown. In the present study, the effects of BYHWD on delayed neuronal death of hippocampus after transient forebrain ischemia were examined in rats. Transient forebrain ischemia in a duration of 15 min was induced with the four-vessel occlusion method. BYHWD (per 6.65 g/kg) was given orally to rats twice each day for 7 days before ischemia. In BYHWD-pretreated rats, the neuronal injury in the hippocampal CA1 region was significantly less than that of controls. Oral administration of BYHWD also markedly attenuated the number of TUNEL-positive neurons and suppressed the expression of caspase-3p20, a product of catalytically active caspase-3, in the CA1 region. Our results suggest that an inhibition of caspase-3 and apoptosis by BYHWD may partially account for its neuroprotection against ischemic injury in the hippocampal CA1 region.

Reorganization of the cochleotopic map in the bat's auditory system by inhibition.

The central auditory system of the mustached bat shows two types of reorganization of cochleotopic (frequency) maps: expanded reorganization resulting from shifts in the best frequencies (BFs) of neurons toward the BF of repetitively stimulated cortical neurons (hereafter centripetal BF shifts) and compressed reorganization resulting from the BF shifts of neurons away from the BF of the stimulated cortical neurons (hereafter centrifugal BF shifts). Facilitation and inhibition evoked by the corticofugal system have been hypothesized to be respectively related to centripetal and centrifugal BF shifts. If this hypothesis is correct, bicuculline (an antagonist of inhibitory GABA-A receptors) applied to cortical neurons would change centrifugal BF shifts into centripetal BF shifts. In the mustached bat, electric stimulation of cortical Doppler-shifted constant-frequency neurons, which are highly specialized for frequency analysis, evokes the centrifugal BF shifts of ipsilateral collicular and cortical Doppler-shifted constant-frequency neurons and contralateral cochlear hair cells. Bicuculline applied to the stimulation site changed the centrifugal BF shifts into centripetal BF shifts. On the other hand, electric stimulation of neurons in the posterior division of the auditory cortex, which are not particularly specialized for frequency analysis, evokes centripetal BF shifts of cortical neurons located near the stimulated cortical neurons. Bicuculline applied to the stimulation site augmented centripetal BF shifts but did not change the direction of the shifts. These observations support the hypothesis and indicate that centripetal and centrifugal BF shifts are both based on a single mechanism consisting of two components: facilitation and inhibition.