
本研究揭示了初級嗅覺皮層（AON 和 Pir）如何調控全腦嗅覺網絡的時空動態，以及它們在健康和老化大腦中對神經活動傳播的影響。


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Odor information is transmitted from the olfactory bulb to several primary olfactory cortical regions in parallel, including the anterior olfactory nucleus (AON) and piriform cortex (Pir). However, the specific roles of the olfactory bulb and cortical outputs in wider interactions with other interconnected regions throughout the brain remain unclear due to the lack of suitable in vivo techniques. Furthermore, emerging associations between olfactory-related dysfunctions and neurological disorders underscore the need for examining olfactory networks at the systems level. Using optogenetics, fMRI, and computational modeling, we interrogated the spatiotemporal properties of brain-wide neural interactions in olfactory networks. We observed distinct downstream recruitment patterns. Specifically, stimulation of excitatory projection neurons in OB predominantly activates primary olfactory network regions, while stimulation of OB afferents in AON and Pir primarily orthodromically activates hippocampal/striatal and limbic networks, respectively. Temporally, repeated OB or AON stimulation diminishes neural activity propagation brain-wide in contrast to Pir stimulation. Dynamic causal modeling analysis reveals a robust inhibitory effect of AON outputs on striatal and limbic network regions. In addition, experiments in aged rat models show decreased brain-wide activation following OB stimulation, particularly in the primary olfactory and limbic networks. Modeling analysis identifies a dysfunctional AON to Pir connection, indicating the impairment of this primary olfactory cortical circuit that disrupts the downstream long-range propagation. Our study for the first time delineates the spatiotemporal properties of olfactory neural activity propagation in brain-wide networks and uncovers the roles of primary olfactory cortical, AON and Pir, outputs in shaping neural interactions at the systems level.

### Competing Interest Statement

The authors have declared no competing interest.

Olfactory cortical outputs recruit and shape distinct brain-wide spatiotemporal networks

嗅覺皮層輸出調控並塑造獨特的全腦時空網絡

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長期暴露於高溫環境中會導致視前區 (POA) 到後室旁丘腦 (pPVT) 神經通路活動異常，進而引發負面情緒和過度興奮狀態。


Mental and behavioral disorders are associated with extended period of hot weather as found in heatwaves, but the underlying neural circuit mechanism is poorly known. The posterior paraventricular thalamus (pPVT) is a hub for emotional processing and receives inputs from the hypothalamic preoptic area (POA), the well-recognized thermoregulation center. The present study was designed to explore whether chronic heat exposure leads to aberrant activities in POA recipient pPVT neurons and subsequent changes in emotional states. By devising an air heating paradigm mimicking the condition of heatwaves and utilizing emotion-related behavioral tests, viral track tracing, in vivo calcium recordings, optogenetic manipulations and electrophysiological recordings, we found that chronic heat exposure for 3 weeks led to negative emotional and hyperarousal states in mice. The pPVT neurons receive monosynaptic excitatory and inhibitory innervations from the POA. These neurons exhibited a persistent increase in neural activity following chronic heat exposure, which was essential for chronic heat-induced emotional changes. Notably, these neurons were also prone to display stronger neuronal activities associated with anxiety responses to stressful situations. Furthermore, we observed saturated neuroplasticity in the POA-pPVT excitatory pathway after chronic heat exposure that occluded further potentiation. Taken together, long-term aberration in the POA to pPVT pathway offers a neurobiological mechanism of emotional and behavioral changes seen in extended period of hot weather like heatwaves.

### Competing Interest Statement

The authors have declared no competing interest.

Repeated activation of preoptic area-recipient neurons in posterior paraventricular nucleus mediates chronic heat-induced negative emotional and hyperarousal states

視前區-後室旁丘腦神經元重複激活介導慢性熱誘導的負面情緒和過度興奮狀態


후각망에서 전구체 출력과 피리폼 피질 출력은 뇌 전체의 시공간적 네트워크를 다르게 모집하고 형성하며, 노화된 뇌에서는 이러한 네트워크의 활성화가 감소하고 연결성이 손상된다.


후각-피질-출력은-뇌-전체의-시공간적-네트워크를-모집하고-형성한다


후각 피질 출력은 뇌 전체의 시공간적 네트워크를 모집하고 형성한다



만성적인 열 노출은 시상후부 시상밑핵(pPVT) 뉴런의 활동을 변화시켜 부정적인 감정과 과각성 상태를 유발한다.


시상후부-시상밑핵에서-시상전핵-수용-뉴런의-반복적-활성화는-만성-열-노출로-인한-부정적-감정-및-과각성-상태를-매개한다


시상후부 시상밑핵에서 시상전핵 수용 뉴런의 반복적 활성화는 만성 열 노출로 인한 부정적 감정 및 과각성 상태를 매개한다



慢性的な熱ストレスは、視床後部室傍核（pPVT）への視索前野（POA）からの興奮性入力の増強と、pPVTニューロンの興奮性亢進を引き起こし、ネガティブ感情や過覚醒状態を引き起こす。


視床後部室傍核における視索前野入力ニューロンの反復活性化は-慢性的な熱ストレスによるネガティブ感情と過覚醒状態を媒介する


視床後部室傍核における視索前野入力ニューロンの反復活性化は、慢性的な熱ストレスによるネガティブ感情と過覚醒状態を媒介する



嗅覚系の一次皮質領域である前嗅核（AON）と梨状皮質（Pir）は、それぞれ海馬/線条体ネットワークと辺縁系ネットワークなど、異なる高次脳ネットワークを動員し、嗅覚情報の処理において異なる役割を果たす。


嗅覚皮質出力は-異なる脳全体の時空間ネットワークを動員し-形成する


嗅覚皮質出力は、異なる脳全体の時空間ネットワークを動員し、形成する



Chronic heat exposure triggers negative emotional responses and hyperarousal in mice by inducing persistent activity changes in the neural pathway connecting the preoptic area (POA) to the posterior paraventricular thalamus (pPVT).


chronic-heat-exposure-induces-negative-emotional-and-hyperarousal-states-in-mice-a-key-role-for-the-preoptic-area-posterior-paraventricular-thalamus-pathway


Chronic Heat Exposure Induces Negative Emotional and Hyperarousal States in Mice: A Key Role for the Preoptic Area-Posterior Paraventricular Thalamus Pathway



本研究では、抑制性基底核出力核である黒質網様部（SNr）と淡蒼球外節（GPe）が、脚橋核（PPN）の細胞種特異的かつ領域特異的な様式で神経支配し、運動と報酬行動に異なる影響を与えることを明らかにした。


The canonical basal ganglia model predicts that the substantia nigra pars reticulata (SNr) and the globus pallidus externa (GPe) will have specific effects on locomotion: the SNr inhibiting locomotion and the GPe enhancing it. In this manuscript, we use in vivo optogenetics to show that a projection-defined neural subpopulation within each structure exerts non-canonical effects on locomotion. These non-canonical subpopulations are defined by their projection to the pedunculopontine nucleus (PPN) and mediate opposing effects on reward. To understand how these structures differentially modulate the PPN, we use ex vivo whole-cell recording with optogenetics to comprehensively dissect the SNr and GPe connections to regionally– and molecularly-defined populations of PPN neurons. The SNr inhibits all PPN subtypes, but most strongly inhibits caudal glutamatergic neurons. The GPe selectively inhibits caudal glutamatergic and GABAergic neurons, avoiding both cholinergic and rostral cells. This circuit characterization reveals non-canonical basal ganglia pathways for locomotion and valence.

![Figure][1]</img>

Graphical Abstract



### Competing Interest Statement

The authors have declared no competing interest.

 [1]: pending:yes

Inhibitory basal ganglia nuclei differentially innervate pedunculopontine nucleus subpopulations and evoke opposite motor and valence behaviors

抑制性基底核は脚橋核のサブタイプに異なる入力様式を示し-運動と情動行動に反対の効果を及ぼす


抑制性基底核は脚橋核のサブタイプに異なる入力様式を示し、運動と情動行動に反対の効果を及ぼす



The substantia nigra pars reticulata (SNr) and globus pallidus externa (GPe) differentially innervate pedunculopontine nucleus (PPN) subpopulations, challenging the canonical basal ganglia model by demonstrating non-canonical roles in locomotion and valence processing.


differential-innervation-of-pedunculopontine-nucleus-subpopulations-by-inhibitory-basal-ganglia-nuclei-reveals-non-canonical-pathways-for-motor-and-valence-behaviors


Differential Innervation of Pedunculopontine Nucleus Subpopulations by Inhibitory Basal Ganglia Nuclei Reveals Non-Canonical Pathways for Motor and Valence Behaviors



人間の脳波は、局所的な活動ではなく、大脳皮質全体にわたる広域的な位相ダイナミクスによって支配されている。


The organization of the phase of electrical activity in the cortex is critical to inter-site communication, but the balance of this communication across macroscopic (>15cm), mesoscopic (1 to 15cm) and microscopic (<1cm) ranges is an open question. Traveling waves in the cortex are spatial phase gradients, such that phase values change smoothly through the cortical sheet over time. Macroscopic cortical traveling waves have been understudied compared to micro- or mesoscopic waves. The spatial frequencies (i.e., the characteristic scales) of cortical waves have been characterized in the grey-matter for micro- and mesoscopic scales of cortex and show decreasing spatial power with increasing spatial frequency. This research, however, has been limited by the size of the measurement array, thus excluding macroscopic traveling waves. Obversely, poor spatial resolution of extra-cranial measurements prevents incontrovertible macroscopic estimates of spatial power via electroencephalogram and magnetoencephalogram. We apply a novel method to estimate the spatial frequency spectrum of phase dynamics in order to quantify the uncertain macroscopic scale. Stereotactic electroencephalogram is utilized to leverage measurements of local-field potentials within the grey matter, while also taking advantage of the sometimes large extent of spatial coverage. Irregular sampling of the cortical sheet is offset by use of linear algebra techniques to empirically estimate the spatial frequency spectrum. We find the spatial power of the phase is highest at the lowest spatial frequencies (longest wavelengths), consistent with the power spectra ranges for micro- and meso-scale dynamics, but here shown up to the size of the measurement array (15-25cm), i.e., approaching the entire extent of cortex. Low spatial frequencies dominate the cortical phase dynamics. This has important functional implications as it means that the phase measured at a single contact in the grey-matter is more strongly a function of global phase organization than local. This result arises across a wide range of temporal frequencies, from the delta band (2Hz) through to the high gamma range (100Hz).

### Competing Interest Statement

The authors have declared no competing interest.

The dominance of global phase dynamics in human cortex, from delta to gamma

大脳皮質における広域位相ダイナミクスの優位性-デルタ波からガンマ波まで


大脳皮質における広域位相ダイナミクスの優位性：デルタ波からガンマ波まで
