Systematic examination of the inputs and outputs of the nonlemniscal auditory thalamus will facilitate the functional elucidation of this complex structure in the central auditory system. In mice, comprehensive tracing studies that reveal the long-range connectivity of the nonlemniscal auditory thalamus are lacking. To this end, we used Cre-inducible anterograde and monosynaptic retrograde viruses in Calbindin-2A-dgCre-D and Calretinin-IRES-Cre mice, focusing on the differences across subdivisions of the nonlemniscal auditory thalamus. We found that, 1) the dorsal and medial parts of the auditory thalamus were predominantly connected to sensory processing centers, whereas the posterior intralaminar (PIN) and peripeduncular nucleus (PP) were additionally connected to emotion and motivation modulation centers; 2) ventral auditory cortical areas were the major source of cortical inputs for all subdivisions, and the PIN/PP received more inputs from cortical layer 5 than other subdivisions did; 3) deep layers of the superior colliculus and rostral part of the nonlemniscal inferior colliculus preferentially projected to the PIN/PP; and 4) compared with the dorsal auditory thalamus, the PIN/PP mainly innervated association cortices. In addition, new brain areas connected to the nonlemniscal auditory thalamus, mostly the PIN/PP, were identified. Our results suggested subdivision-specific function of the nonlemniscal auditory thalamus in sound processing.

Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.

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This paper presents the design of a wireless, implantable, multi-channel, programmable stimulator with arbitrary channel combination. A novel channel management module using a switch array is presented, enabling arbitrary channel configuration with a silicon area reduction of 81%. The chip was fabricated in a 0.18-μm Taiwan semiconductor manufacturing company (TSMC) high voltage (HV) complementary metal–oxide semiconductor (CMOS) technology. A stimulator system was realized using the proposed integrated circuit (IC). A wireless communication link was established between a specified Android-based graphical user interface (GUI) and the proposed device for control of the stimulation pattern and wireless battery charging. The size of the entire system occupies a volume of only 14 mm × 14 mm × 4 mm (without the battery). Experimental results demonstrated a successful independent configuration between different channels, as well as an arbitrary channel combination, as expected.

The protracted maturational process of temporal processing in layer 4 (L4) of primary auditory cortex (A1) has been extensively studied. Accumulating evidences show that layer 5 (L5) receives direct thalamic inputs as well. How the temporal responses in L5 may developmentally emerge remains unclear. Using in vivo loose-patch recordings in rat A1, we found that putative pyramidal (Pyr) neurons in developing L5 exhibited adult-like stimulus-following ability but less bursting shortly after hearing onset. L5 Pyr neurons in adult A1 exhibited phase-locking similar to L4 neurons, while L5 fast-spiking (FS) neurons showed greater phase-locking at 7 and 12.5 pps. In developing L5, whole-cell recordings revealed inhibition with decay constant comparable to that in adult L5, thereby avoiding the summation of inhibition that contributed to the strong adaptation in L4. Given the targets of L5 outputs, the relatively precocious temporal processing in L5 might contribute to temporal response maturation in connected cortical and subcortical areas. Our findings were in agreement with the idea that L5 may be a "hub" for processing cortical inputs and outputs that can operate independently of L4.

Microglial abnormalities may contribute to neurodevelopmental disorders. PTEN is implicated as a susceptibility gene for autism spectrum disorders and its germline ablation in mice causes behavioral abnormalities. Here we find postnatal PTEN deletion in microglia causes deficits in sociability and novel object recognition test. Mutant mice harbor markedly more activated microglia that manifest enhanced phagocytosis. Interestingly, two-week postponement of microglia PTEN ablation leads to no social interaction defects, even though mutant microglia remain abnormal in adult animals. Disturbed neurodevelopment caused by early PTEN deletion in microglia is characterized by insufficient VGLUT1 protein in synaptosomes, likely a consequence of enhanced removal by microglia. In correlation, in vitro acute slice recordings demonstrate weakened synaptic inputs to layer 5 pyramidal neurons in the developing cortex. Therefore, microglial PTEN safeguards integrity of neural substrates underlying sociability in a developmentally determined manner.

Alterations in internal states, such as elevated arousal level and increased anxiety or fear, triggered by alerting environmental cues are required for behavioral state transitions promoting survival. However, the specific brain region that plays an interfacing role between alerting stimuli and internal states remains to be identified. Here, we report that the medial sector of the auditory thalamus (ATm), which consists of a group of non-lemniscal thalamic nuclei, can fulfill this function. VGluT2-expressing ATm (ATmVGluT2+) neurons receive direct and strong inputs from both visual and auditory midbrain regions, and project to multiple downstream structures critically involved in brain state regulation. Their activity was correlated with, and indispensable for, both blue light- and sound-induced NREM sleep-to-Wake transition, and their arousing effects were mainly mediated by, but not limited to, the temporal association cortices. ATmVGluT2+ neuron activation in awake behaving mice induced pupil dilation and behavioral responses suggestive of anxiety. Blocking the neurotransmitter release of ATmVGluT2+ neurons receiving auditory inputs selectively abolished loud noise-triggered escape behavior but not locomotion. Thus, the ATm is an interface in mouse brain that can transform alerting environmental cues into internal arousal and emotional state alterations that promote survival.