RETRACTED: Insular cortex processes aversive somatosensory information and is crucial for threat learning

Abstract

Learning about threats is essential for survival. During threat learning, an innocuous sensory percept such as a tone acquires an emotional meaning when paired with an aversive stimulus such as a mild footshock. The amygdala is critical for threat memory formation, but little is known about upstream brain areas that process aversive somatosensory information. Using optogenetic techniques in mice, we found that silencing of the posterior insula during footshock reduced acute fear behavior and impaired 1-day threat memory. Insular cortex neurons respond to footshocks, acquire responses to tones during threat learning, and project to distinct amygdala divisions to drive acute fear versus threat memory formation. Thus, the posterior insula conveys aversive footshock information to the amygdala and is crucial for learning about potential dangers in the environment.

Singing training predicts increased insula connectivity with speech and respiratory sensorimotor areas at rest

“…We found increased connectivity in conservatory trained singers between bilateral PI and lobule VI of the cerebellum, a somatotopically organized sensorimotor region that receives somatosensory afferents from the vocal tract and sends out efferents to motor areas Grodd et al, 2001;O'Reilly et al, 2010;Stoodley and Schmahmann, 2010), including those engaged in speaking and singing (Brown et al, 2004;Brown et al, 2006). This is consistent with the unique profile of the PI, which is predominantly associated with sensorimotor processes and the interoceptive representation of visceral and sensory feelings from the body (Berret et al, 2019;Chang et al, 2013;Craig, 2002;Olausson et al, 2002;Pugnaghi et al, 2011;Segerdahl et al, 2015), including orofacial regions (Ikenoue et al, 2018;Sato et al, 2017;Tsutsumi et al, 2018;Yoshida et al, 2017).…”

“…In a general context, the insular cortex is functionally and structurally connected to a vast number of cortical and subcortical brain regions subserving sensory, emotional, motivational and cognitive processes (Gogolla, 2017;Nomi et al, 2018). As an actively participating integration hub within these networks, its multifaceted functional roles range from conscious and non-conscious integration of bodily information (Craig, 2002(Craig, , 2009Critchley et al, 2004;Karnath and Baier, 2010;Olausson et al, 2002), the preservation of homeostatic states in autonomic systems that are critical to body regulation (Gu and FitzGerald, 2014;Strigo and Craig, 2016), to salience detection and valence assessment of incoming sensory inputs (Berret et al, 2019;Singer et al, 2009), as well as the coordination of large-scale network dynamics associated with higher-level cognitive processes (Menon and Uddin, 2010;Seeley et al, 2007;Uddin, 2015). Speech specific clinical and functional imaging data suggest a bilateral engagement for linguistic processes and a lefthemispheric dominance for non-linguistic aspects of speech-related perceptual and motor processes in the dorsal anterior insula (Ackermann and Riecker, 2010;Oh et al, 2014).…”

Dopamine in the basal amygdala signals salient somatosensory events during fear learning

“…All other procedures were the same between the control -and the test groups. Stereotaxic surgeries with a model 940 stereotactic instrument (Kopf Instruments, USA) followed the procedures described in Berret et al (2019). Virus suspension (200 -400 nl) was injected unilaterally into the VTA at coordinates relative to bregma: AP -3.3 mm; ML -0.35 mm; DV 4.2-4.6 mm (DV measured from the dura surface).…”

“…Fiber optic implants for in-vivo optogenetic silencing were custom made from a 200 µm core / 0.39 NA / 230 m outer diameter optic fiber (FT200EMT; Thorlabs) and 1.25 mm outer diameter ceramic ferrules (CFLC230; Thorlabs) as described (Sparta et al, 2012). Yellow light was produced by a 561 nm diode pumped solid state (DPSS) laser (MGL-FN-561-AOM-100mW, CNI Lasers, China) equipped with an AOM and an additional mechanical shutter (SHB05T; Thorlabs) as described previously (Berret et al, 2019). The laser power was adjusted to 10 mW after the implant tip for each individual animal.…”

“…Indeed, footshock stimulation causes cfos expression in a sparse, but distinct neuronal population in the LA and BA (Gore et al, 2015). Furthermore, we have recently identified a glutamatergic synaptic input from the insular cortex as a candidate pathway for one such "depolarizing" teaching signal in the LA (Berret et al, 2019).…”