关键词: Electrical stimulation Excitation Inferior colliculus Optogenetics Prefrontal cortex

Mesh : Animals Inferior Colliculi / physiology Somatosensory Cortex / physiology Optogenetics Electric Stimulation Auditory Cortex / physiology Motor Cortex / physiology Auditory Pathways / physiology Synapses / physiology Male Neurons / physiology Rats, Sprague-Dawley Green Fluorescent Proteins / genetics metabolism Female Channelrhodopsins / metabolism genetics Rats

来  源:   DOI:10.1016/j.heares.2024.109009

Abstract:
We recently reported that the central nucleus of the inferior colliculus (the auditory midbrain) is innervated by glutamatergic pyramidal cells originating not only in auditory cortex (AC), but also in multiple \'non-auditory\' regions of the cerebral cortex. Here, in anaesthetised rats, we used optogenetics and electrical stimulation, combined with recording in the inferior colliculus to determine the functional influence of these descending connections. Specifically, we determined the extent of monosynaptic excitation and the influence of these descending connections on spontaneous activity in the inferior colliculus. A retrograde virus encoding both green fluorescent protein (GFP) and channelrhodopsin (ChR2) injected into the central nucleus of the inferior colliculus (ICc) resulted in GFP expression in discrete groups of cells in multiple areas of the cerebral cortex. Light stimulation of AC and primary motor cortex (M1) caused local activation of cortical neurones and increased the firing rate of neurones in ICc indicating a direct excitatory input from AC and M1 to ICc with a restricted distribution. In naïve animals, electrical stimulation at multiple different sites within M1, secondary motor, somatosensory, and prefrontal cortices increased firing rate in ICc. However, it was notable that stimulation at some adjacent sites failed to influence firing at the recording site in ICc. Responses in ICc comprised singular spikes of constant shape and size which occurred with a short, and fixed latency (∼ 5 ms) consistent with monosynaptic excitation of individual ICc units. Increasing the stimulus current decreased the latency of these spikes, suggesting more rapid depolarization of cortical neurones, and increased the number of (usually adjacent) channels on which a monosynaptic spike was seen, suggesting recruitment of increasing numbers of cortical neurons. Electrical stimulation of cortical regions also evoked longer latency, longer duration increases in firing activity, comprising multiple units with spikes occurring with significant temporal jitter, consistent with polysynaptic excitation. Increasing the stimulus current increased the number of spikes in these polysynaptic responses and increased the number of channels on which the responses were observed, although the magnitude of the responses always diminished away from the most activated channels. Together our findings indicate descending connections from motor, somatosensory and executive cortical regions directly activate small numbers of ICc neurones and that this in turn leads to extensive polysynaptic activation of local circuits within the ICc.
摘要:
我们最近报道,下丘(听觉中脑)的中央核受到谷氨酸能锥体细胞的神经支配,这些细胞不仅起源于听觉皮层(AC),但也在大脑皮层的多个“非听觉”区域。这里,在麻醉的老鼠身上,我们用光遗传学和电刺激,结合在下丘的记录,以确定这些下降连接的功能影响。具体来说,我们确定了单突触兴奋的程度以及这些下降连接对下丘自发活动的影响。将编码绿色荧光蛋白(GFP)和通道视紫红质(ChR2)的逆行病毒注入下丘(ICc)的中央核,导致GFP在大脑皮层多个区域的离散细胞群中表达。AC和初级运动皮层(M1)的光刺激引起皮层神经元的局部激活,并增加了ICc中神经元的放电率,表明从AC和M1到ICc的直接兴奋性输入具有有限的分布。在幼稚的动物中,M1内多个不同部位的电刺激,次级电机,体感,前额皮质增加了ICc的放电率。然而,值得注意的是,在ICc中,一些邻近部位的刺激未能影响记录部位的点火。ICc中的响应包括形状和大小恒定的奇异尖峰,和与单个ICc单元的单突触激发一致的固定潜伏期(~5ms)。增加刺激电流减少了这些尖峰的延迟,表明皮质神经元的去极化更快,并增加了看到单突触尖峰的(通常是相邻的)通道的数量,提示皮质神经元数量的增加。皮层区域的电刺激也会引起更长的潜伏期,射击活动持续时间更长,包括多个单元,这些单元的尖峰出现明显的时间抖动,与多突触兴奋一致。增加刺激电流增加了这些多突触反应中的尖峰数量,并增加了观察到反应的通道数量,尽管响应的幅度总是在远离最激活的通道时减弱。我们的发现一起表明电机的下降连接,体感和执行皮层区域直接激活少量的ICc神经元,这反过来又导致ICc内局部回路的广泛多突触激活。
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