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.
Cortical sensory processing is modulated by behavioral and cognitive states. How this modulation is achieved by changing synaptic circuits remains largely unknown. In awake mouse auditory cortex, we ...found that sensory-evoked spike responses of layer 2/3 (L2/3) excitatory cells were scaled down with preserved sensory tuning when mice transitioned from quiescence to active behaviors, including locomotion, whereas L4 and thalamic responses were unchanged. Whole-cell voltage-clamp recordings revealed that tone-evoked synaptic excitation and inhibition exhibited a robust functional balance. The change to active states caused scaling down of excitation and inhibition at approximately equal levels in L2/3 cells, but resulted in no synaptic changes in L4 cells. This lamina-specific gain control could be attributed to an enhancement of L1-mediated inhibitory tone, with L2/3 parvalbumin inhibitory neurons also being suppressed. Thus, L2/3 circuits can adjust the salience of output in accordance with momentary behavioral demands while maintaining the sensitivity and quality of sensory processing.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
There have been numerous studies on the relationship between sleep and depression, as well as the relationship between sleep and depression, and heart rate variability (HRV), respectively. Even so, ...few studies have combined 24-h HRV analysis to study sleep quality and depressive symptoms. The purpose of this cross-sectional study was to investigate the relationship between depressed symptoms, sleep quality, and 24-h HRV in medical students. The particiants were all students at a medical university in Guangdong province, China. A total of 74 college students participated. They were asked to complete a questionnaire that included the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Inventory-II (BDI-II), the Positive and Negative Affect Scale (PANAS), and 24-h ECG monitoring. The results showed that 41.7% of the medical students had poor sleep quality, with higher levels of depressive symptoms and more negative emotions, and there was no difference in 24-h HRV indices between the low PSQI group and the high one. Correlation analysis showed that there was a significant relationship between sleep quality and depressive symptoms (
= 0.617), but the relationship between 24-h HRV indices and PSQI global scores, BDI scores were not significant. However, the correlation analysis of PSQI components and 24-h HRV showed that sleep disturbance was significantly negatively correlated with SDNN and LF in waking period (
= -0.285, -0.235), and with SDNN in sleeping period (
= -0.317). In general, the sleep disturbance in PSQI components can sensitively reflect the relationship between sleep quality and 24-h HRV of medical students. Individuals with higher sleep disturance may have lower SDNN during awake period and bedtime period, and lower LF in awake period. Twenty-four hour HRV has certain application value in clinical sleep quality monitoring, and its sensitivity and specificity in clinical application and daily life are still worth further investigation.
The relationship between forbearance, a psychological resource, and depression has to date remained inconclusive. The present study investigated heart rate variability (HRV) reactivity to acute ...stressor tasks in participants with different levels of forbearance to discover how forbearance influences depressive emotions when facing adversity.
The study examined the relationship between forbearance and depression, comparing HRV reactivity to stressor tasks in participants with different levels of forbearance. The levels of reported forbearance were assessed by the Forbearance Scale (FS). The Patient Health Questionnaire-9 (PHQ-9) was used to assessed depression severity. HRV reactivity was evaluated at five stages: baseline, the active stressor task, the period of recovery after the active stressor task, the passive stressor task, the period of recovery after the passive stressor task.
FS scores had a significant negative correlation with PHQ-9 and a significant positive correlation with HRV; significant differences existed between the basal HRV in the higher and lower FS groups. In the passive stressor task and the period of recovery after the active stressor task, significantly different HRV responses were identified between the two groups.
Forbearance was correlated with depression and HRV. The present research found differences in HRV among subjects with different levels of forbearance in the baseline as well as stressor and recovery periods, suggesting that self-regulation dysfunction may exist among persons with lower levels of forbearance. Because of the higher levels of forbearance, the negative emotions of individuals caused by adversity are mitigated.
The hippocampus has been thought to process auditory information. However, the properties, pathway, and role of hippocampal auditory responses are unclear. With loose-patch recordings, we found that ...hippocampal neurons are mainly responsive to noise and are not tonotopically organized. Their latencies are shorter than those of primary auditory cortical (A1) neurons but longer than those of medial septal (MS) neurons, suggesting that hippocampal auditory information comes from MS neurons rather than from A1 neurons. Silencing the MS blocks both hippocampal auditory responses and memory of auditory fear conditioning trained with noise and tone. Auditory fear conditioning was associated with some cues but not with a specific frequency of sound, as demonstrated by animals trained with noise, 2.5-, 5-, 10-, 15-, or 30-kHz tones, and tested with these sounds. Therefore, the noise responses of hippocampal neurons have identified a population of neurons that can be associated with auditory fear conditioning.
The relationship between anxiety and sleep disorders is a key research topic in the academic community. However, evidence on the mechanism through which anxiety influences sleep disorders remains ...limited. The purpose of this study was to investigate the roles of flourishing and neuroticism in the mechanism through which anxiety influences sleep disorders in medical students. We constructed a moderated mediation model and tested the mediating role of flourishing and the moderating role of neuroticism in medical college students. The results showed that: (1) anxiety was significantly and positively related to sleep disorders and significantly and negatively related to flourishing; flourishing was significantly and negatively related to sleep disorders; neuroticism was significantly and positively related to sleep disorders; (2) flourishing had a mediation effect on the relationship between anxiety and sleep disorders; (3) neuroticism moderated the process through which flourishing mediated the effect of anxiety on sleep disorders. Our research expands the literature on the mechanism underlying the effects of anxiety on sleep disorders and provides insights into the potential prevention and intervention of sleep and emotional problems in medical students.
Sensory information undergoes ordered and coordinated processing across cortical layers. Whereas cortical layer (L) 4 faithfully acquires thalamic information, the superficial layers appear well ...staged for more refined processing of L4-relayed signals to generate corticocortical outputs. However, the specific role of superficial layer processing and how it is specified by local synaptic circuits remains not well understood. Here, in the mouse primary auditory cortex, we showed that upper L2/3 circuits play a crucial role in refining functional selectivity of excitatory neurons by sharpening auditory tonal receptive fields and enhancing contrast of frequency representation. This refinement is mediated by synaptic inhibition being more broadly recruited than excitation, with the inhibition predominantly originating from interneurons in the same cortical layer. By comparing the onsets of synaptic inputs as well as of spiking responses of different types of neuron, we found that the broadly tuned, fast responding inhibition observed in excitatory cells can be primarily attributed to feedforward inhibition originating from parvalbumin (PV)-positive neurons, whereas somatostatin (SOM)-positive interneurons respond much later compared with the onset of inhibitory inputs to excitatory neurons. We propose that the feedforward circuit-mediated inhibition from PV neurons, which has an analogous function to lateral inhibition, enables upper L2/3 excitatory neurons to rapidly refine auditory representation.
The inferior colliculus (IC) is a critical centre for the binaural processing of auditory information. However, previous studies have mainly focused on the central nucleus of the inferior colliculus ...(ICC), and less is known about the dorsal nucleus of the inferior colliculus (ICD). Here, we first examined the characteristics of the neuronal responses in the mouse ICD and compared them with those in the inferior colliculus under binaural and monaural conditions using
loose-patch recordings. ICD neurons exhibited stronger responses to ipsilateral sound stimulation and better binaural summation than those of ICC neurons, which indicated a role for the ICD in binaural hearing integration. According to the abundant interactions between bilateral ICDs detected using retrograde virus tracing, we further studied the effect of unilateral ICD silencing on the contralateral ICD. After lidocaine was applied, the responses of some ICD neurons (13/26), especially those to ipsilateral auditory stimuli, decreased. Using whole-cell recording and optogenetic methods, we investigated the underlying neuronal circuits and synaptic mechanisms of binaural auditory information processing in the ICD. The unilateral ICD provides both excitatory and inhibitory projections to the opposite ICD, and the advantaged excitatory inputs may be responsible for the enhanced ipsilateral responses and binaural summation of ICD neurons. Based on these results, the contralateral ICD might modulate the ipsilateral responses of the neurons and binaural hearing.
Functional receptive fields of neurons in sensory cortices undergo progressive refinement during development. Such refinement may be attributed to the pruning of non-optimal excitatory inputs, ...reshaping of the excitatory tuning profile through modifying the strengths of individual inputs, or strengthening of cortical inhibition. These models have not been directly tested because of the technical difficulties in assaying the spatiotemporal patterns of functional synaptic inputs during development. Here we apply in vivo whole-cell voltage-clamp recordings to the recipient layer 4 neurons in the rat primary auditory cortex (A1) to determine the developmental changes in the frequency-intensity tonal receptive fields (TRFs) of their excitatory and inhibitory inputs. Surprisingly, we observe co-tuned excitation and inhibition immediately after the onset of hearing, suggesting that a tripartite thalamocortical circuit with relatively strong feedforward inhibition is formed independently of auditory experience. The frequency ranges of tone-driven excitatory and inhibitory inputs first expand within a few days of the onset of hearing and then persist into adulthood. The latter phase is accompanied by a sharpening of the excitatory but not inhibitory frequency tuning profile, which results in relatively broader inhibitory tuning in adult A1 neurons. Thus the development of cortical synaptic TRFs after the onset of hearing is marked by a slight breakdown of previously formed excitation-inhibition balance. Our results suggest that functional refinement of cortical TRFs does not require a selective pruning of inputs, but may depend more on a fine adjustment of excitatory input strengths.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Urethane has little effect on nervous system and is often used in neuroscience studies. However, the effect of urethane in neurons is not thoroughly clear. In this study, we investigated changes in ...neuron responses to tones in inferior colliculus during urethane anesthesia. As urethane was metabolized, the best and characteristic frequencies did not obviously change, but the minimal threshold (MT) remained relatively stable or was elevated. The frequency tuning bandwidth at 60 dB SPL (BW
60dBSPL
) remained unchanged or decreased, and the average evoked spike of effective frequencies at 60 dB SPL (ES
60dBSPL
) gradually decreased. Although the average evoked spike of effective frequencies at a tone intensity of 20 dB SPL above MT (ES
20dBSPLaboveMT
) decreased, the frequency tuning bandwidth at a tone intensity of 20 dB SPL above MT (BW
20dBSPLaboveMT
) did not change. In addition, the changes in MT, ES
60dBSPL
, BW
60dBSPL
, and ES
20dBSPLaboveMT
increased with the MT in pre-anesthesia awake state (MT
pre−anesthesiaawake
). In some neurons, the MT was lower, BW
60dBSPL
was broader, and ES
60dBSPL
and ES
20dBSPLaboveMT
were higher in urethane anesthesia state than in pre-anesthesia awake state. During anesthesia, the inhibitory effect of urethane reduced the ES
20dBSPLaboveMT
, but did not change the MT, characteristic frequency, or BW
20dBSPLaboveMT
. In the recording session with the strongest neuron response, the first spike latency did not decrease, and the spontaneous spike did not increase. Therefore, we conclude that urethane can reduce/not change the MT, increase the evoked spike, or broaden/not change the frequency tuning range, and eventually improve the response of auditory neurons to tone with or without “pushing down” the tonal receptive field in thresholding model. The improved effect increases with the MT
pre−anesthesiaawake
of neurons. The changes induced by the inhibitory and improved effects of urethane abide by similar regularities, but the change directions are contrary. The improvement mechanism may be likely due to the increase in the ratio of excitatory/inhibitory postsynaptic inputs to neurons.
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