Summary Cross-modality interaction in sensory perception is advantageous for animals’ survival. How cortical sensory processing is cross-modally modulated and what are the underlying neural circuits remain poorly understood. In mouse primary visual cortex (V1), we discovered that orientation selectivity of layer (L)2/3 but not L4 excitatory neurons was sharpened in the presence of sound or optogenetic activation of projections from primary auditory cortex (A1) to V1. The effect was manifested by decreased average visual responses yet increased responses at the preferred orientation. It was more pronounced at lower visual contrast, and was diminished by suppressing L1 activity. L1 neurons were strongly innervated by A1-V1 axons and excited by sound, while visual responses of L2/3 vasoactive intestinal peptide (VIP) neurons were suppressed by sound, both preferentially at the cell's preferred orientation. These results suggest that the cross-modality modulation is achieved primarily through L1 neuron and L2/3 VIP-cell mediated inhibitory and disinhibitory circuits.

The nuclear factor erythroid 2-related factor 2 and antioxidant-response element (Nrf2-ARE) pathway is a key regulator for modulating inflammation and oxidative damage, which are involved in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Previous studies have demonstrated that Nrf2-ARE pathway play neural protective roles in traumatic brain injury, cerebral ischemia, and intracerebral hemorrhage models; however, it has not been investigated whether, and to what degree, the Nrf2-ARE pathway is induced by SAH, and the role of the Nrf2-ARE pathway in development of EBI following SAH remains unknown. Experiment 1 sought to investigate the time course of Nrf2-ARE activation in the cortex in the early stage of SAH. In experiment 2, we assessed the effect of sulforaphane (SUL; a specific Nrf2 activator) on regulation of the Nrf2-ARE pathway in the SAH model and evaluated the impact of SUL on EBI after SAH. The rat SAH model was used injection of 0.3 ml fresh arterial, nonheparinized blood into the prechiasmatic cistern over 20 sec. As a result, Nrf2 and its target gene product, heme oxygenase-1 (HO-1), were up-regulated in the cortex after SAH and peaked at 24 hr post-SAH. After intraperitoneal SUL administration, the elevated expression of Nrf2-ARE-related factors such as Nrf2, HO-1, NAD(P)H:quinone oxidoreductase 1 (NQO1), and glutathione S-transferase-α1 (GST-α1) was detected in the cortex at 48 hr following blood injection. In the SUL-treated group, early brain damage such as brain edema, blood-brain barrier (BBB) impairment, cortical apoptosis, and motor deficits was significantly ameliorated compared with vehicle-treated SAH rats. Our results suggest that the Nrf2-ARE pathway is activated in the brain after SAH, playing a beneficial role in EBI development, possibly through inhibiting cerebral oxidative stress by inducing antioxidant and detoxifying enzymes.

Lateral posterior nucleus (LP) of thalamus, the rodent homologue of primate pulvinar, projects extensively to sensory cortices. However, its functional role in sensory cortical processing remains largely unclear. Here, bidirectional activity modulations of LP or its projection to the primary auditory cortex (A1) in awake mice reveal that LP improves auditory processing in A1 supragranular-layer neurons by sharpening their receptive fields and frequency tuning, as well as increasing the signal-to-noise ratio (SNR). This is achieved through a subtractive-suppression mechanism, mediated largely by LP-to-A1 axons preferentially innervating specific inhibitory neurons in layer 1 and superficial layers. LP is strongly activated by specific sensory signals relayed from the superior colliculus (SC), contributing to the maintenance and enhancement of A1 processing in the presence of auditory background noise and threatening visual looming stimuli respectively. Thus, a multisensory bottom-up SC-pulvinar-A1 pathway plays a role in contextual and cross-modality modulation of auditory cortical processing.

Highlights d LP enhances feature selectivity in V1 by providing subtractive surround suppression d This suppression is mediated by LP innervation of layer 1 inhibitory neurons in V1 d The bottom-up retina-SC-LP-V1 pathway constructs a differential visual circuit d LP helps V1 maintain its orientation selectivity under varying noise background Authors

Our previous study concerning brain trauma has shown that progesterone could regulate toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) signaling pathway in the brain, which also has been proved to play important roles in early brain injury (EBI) after subarachnoid hemorrhage (SAH). The aim of the current study was to investigate whether progesterone administration modulated TLR4/NF-κB pathway signaling pathway in the brain at the early stage of SAH. All SAH animals were subjected to injection of 0.3 ml fresh arterial, non-heparinized blood into prechiasmatic cistern in 20 seconds. Male rats were given 0 or 16 mg/kg injections of progesterone at post-SAH hours 1, 6, and 24. Brain samples were extracted at 48 h after SAH. As a result, SAH could induce a strong up-regulation of TLR4, NF-κB, pro-inflammatory cytokines, MCP-1, and ICAM-1 in the cortex. Administration of progesterone following SAH could down-regulate the cortical levels of these agents related to TLR4/NF-κB signaling pathway. Post-SAH progesterone treatment significantly ameliorated the EBI, such as the clinical behavior scale, brain edema, and blood-brain barrier (BBB) impairment. It was concluded that post-SAH progesterone administration may attenuate TLR4/NF-κB signaling pathway in the rat brain following SAH.

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