A cerebellum-like circuit in the auditory system cancels responses to self-generated sounds

Singla, Shobhit; Dempsey, Conor; Warren, Richard; Enikolopov, Armen G.; Sawtell, Nathaniel B.

doi:10.1038/nn.4567

Cited by 107 publications

(106 citation statements)

References 48 publications

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“…390Furthermore, our data support the 'adaptive filter' theory of the cerebellum, where 391 broadband MF input is differentially filtered by GCs(Dean et al, 2010; Fujita, 392 1982;Singla et al, 2017). Within this framework, our data indicate a gradient in 393 the band-pass filtering properties of GCs.…”

supporting

confidence: 56%

Gradients in the cerebellar cortex enable Fourier-like transformation and improve storing capacity

Straub¹,

Witter

Eshra³

et al. 2019

Preprint

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20Cerebellar granule cells (GCs) making up majority of all the neurons in the 21 vertebrate brain, but heterogeneities among GCs and potential functional 22 consequences are poorly understood. Here, we identified unexpected gradients 23 in the biophysical properties of GCs. GCs closer to the white matter (inner-zone 24 GCs) had higher firing thresholds and could sustain firing with larger current 25 inputs. Dynamic clamp experiments showed that inner-and outer-zone GCs 26 preferentially respond to high-and low-frequency mossy fiber inputs, 27 respectively, enabling to disperse the mossy fiber input into its frequency 28 components as performed by a Fourier transformation. Furthermore, inner-zone 29GCs have faster axonal conduction velocity and elicit faster synaptic potentials in 30 Purkinje cells. Neuronal network modeling revealed that these gradients improve 31 spike-timing precision of Purkinje cells and decrease the number of GCs required 32 to learn spike-sequences. Thus, our study uncovers biophysical gradients in the 33 cerebellar cortex enabling a Fourier-like transformation of mossy fiber inputs. 34Controlling the timing and precision of movements is considered to be one of the 52 main functions of the cerebellum. In the cerebellum, the firing frequency of 53Purkinje cells (PCs) (Heiney et al., 2014;Herzfeld et al., 2015; Hewitt et al., 54 2011;Medina and Lisberger, 2007;Payne et al., 2019; Sarnaik and Raman, 55 2018;Witter et al., 2013) or the timing of spikes (Brown and Raman, 2018; 56 Sarnaik and Raman, 2018) have been shown to be closely related to movement. 57Indeed, cerebellar pathology impairs precision in motor learning tasks (Gibo et 58 al., 2013;Martin et al., 1996) and timing of rhythmic learning tasks (Keele and 59 Ivry, 1990). These functions are executed by a remarkably simple neuronal 60 network architecture. Inputs from mossy fibers (MFs) are processed by GCs and 61 transmitted via their parallel fiber (PF) axons to PCs, which provide the sole 62 output from the cerebellar cortex. GCs represent the first stage in cerebellar 63 processing and have been proposed to provide pattern separation and 64 3 conversion into a sparser representation of the MF input (recently reviewed by 65 (Cayco-Gajic and Silver, 2019). These MF inputs show a wide variety of signaling 66 frequencies, ranging from slow modulating activity to kilohertz bursts of activity 67 (Arenz et al., 2008;Rancz et al., 2007; Ritzau-Jost et al., 2014; van Kan et al., 68 1993). Interestingly, in cellular models of the cerebellum, each MF is considered 69 to be either active or inactive with little consideration for this wide range of 70 frequencies (Albus, 1971;Marr, 1969). Furthermore, in these models, GCs are 71 generally considered as a uniform population of neurons. 72 Here we show that the biophysical properties of GCs differ according to their 73 vertical position in the GC layer. GCs located close to the white matter (inner-74 zone) selectively transmit high-frequency MF inputs, have shorter action 75 poten...

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supporting

confidence: 56%

Gradients in the cerebellar cortex enable Fourier-like transformation and improve storing capacity

Straub¹,

Witter

Eshra³

et al. 2019

Preprint

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“…In the fusiform-cell circuit, multi-modal inputs induce context-dependent changes through STDP (34). Auditory-somatosensory integration in DCN constitutes an adaptive filtering process through which perception of behaviorally-relevant sounds is amplified and internally-generated sounds are attenuated (17, 35, 36). Fusiform-cell synchrony regulation by STDP likely contributes to this perceptual task, while dysregulated multimodal STDP gives rise to phantom perception, as we show here.…”

Section: Discussionmentioning

confidence: 99%

Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans

et al. 2018

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The dorsal cochlear nucleus is the first site of multisensory convergence in mammalian auditory pathways. Principal output neurons, the fusiform cells, integrate auditory-nerve inputs from the cochlea with somatosensory inputs from the head and neck. In previous work, we developed a guinea pig model of tinnitus produced by noise exposure and showed that the fusiform cells in these animals exhibited increased spontaneous activity and cross-unit synchrony, which are physiological correlates of tinnitus. Here, we delivered repeated bimodal auditory-somatosensory stimulation to the dorsal cochlear nucleus of guinea pigs with tinnitus, choosing a stimulus interval known to induce long-term depression (LTD). Twenty minutes per day of LTD-targeting bimodal (but not unimodal) stimulation reduced physiological and behavioral evidence of tinnitus in the guinea pigs after 25 days. Next, we applied the same bimodal treatment to 20 human subjects with tinnitus using a double-blinded, sham-controlled, crossover study. Twenty-eight days of LTD-targeted bimodal stimulation reduced tinnitus loudness and intrusiveness. Unimodal auditory stimulation did not deliver either benefit. Bimodal auditory-somatosensory stimulation that targets LTD in the dorsal cochlear nucleus may hold promise for suppressing chronic tinnitus, which reduces quality of life for millions of tinnitus sufferers worldwide.

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“…Indeed, neural activity in the cerebellum has been linked to the processing of acoustic signals (Baumann & Mattingley, 2010;Jen & Schlegel, 1980;Singla, Dempsey, Warren, Enikolopov, & Sawtell, 2017) and is consistent with the role of this brain structure as an adaptive filter that tracks patterns of predicted and observed sensory input Paulin, 1993;Ridgway, 2000). We therefore next explored whether vocal repertoire (measured as tonal range and tonal complexity; May-Collado et al, 2007) was associated with CB or CX mass.…”

Section: Discussionmentioning

confidence: 73%

“…Cerebellar expansion is also shared among mammals with pronounced auditory adaptations, including echolocating bats and odontocetes, and elephants, which utilize long‐distance infrasonic vocalizations (Hanson, Grisham, Sheh, Annese, & Ridgway, ; Maseko et al, ; Paulin, ). Indeed, neural activity in the cerebellum has been linked to the processing of acoustic signals (Baumann & Mattingley, ; Jen & Schlegel, ; Singla, Dempsey, Warren, Enikolopov, & Sawtell, ) and is consistent with the role of this brain structure as an adaptive filter that tracks patterns of predicted and observed sensory input (Marino et al, ; Paulin, ; Ridgway, ). We therefore next explored whether vocal repertoire (measured as tonal range and tonal complexity; May‐Collado et al, ) was associated with CB or CX mass.…”

Section: Discussionmentioning

confidence: 81%

Co‐evolution of cerebral and cerebellar expansion in cetaceans

Muller

Montgomery

2019

J of Evolutionary Biology

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Cetaceans possess brains that rank among the largest to have ever evolved, either in terms of absolute mass or relative to body size. Cetaceans have evolved these huge brains under relatively unique environmental conditions, making them a fascinating case study to investigate the constraints and selection pressures that shape how brains evolve. Indeed, cetaceans have some unusual neuroanatomical features, including a thin but highly folded cerebrum with low cortical neuron density, as well as many structural adaptations associated with acoustic communication. Previous reports also suggest that at least some cetaceans have an expanded cerebellum, a brain structure with wide‐ranging functions in adaptive filtering of sensory information, the control of motor actions, and cognition. Here, we report that, relative to the size of the rest of the brain, both the cerebrum and cerebellum are dramatically enlarged in cetaceans and show evidence of co‐evolution, a pattern of brain evolution that is convergent with primates. However, we also highlight several branches where cortico‐cerebellar co‐evolution may be partially decoupled, suggesting these structures can respond to independent selection pressures. Across cetaceans, we find no evidence of a simple linear relationship between either cerebrum and cerebellum size and the complexity of social ecology or acoustic communication, but do find evidence that their expansion may be associated with dietary breadth. In addition, our results suggest that major increases in both cerebrum and cerebellum size occurred early in cetacean evolution, prior to the origin of the major extant clades, and predate the evolution of echolocation.

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A cerebellum-like circuit in the auditory system cancels responses to self-generated sounds

Cited by 107 publications

References 48 publications

Gradients in the cerebellar cortex enable Fourier-like transformation and improve storing capacity

Gradients in the cerebellar cortex enable Fourier-like transformation and improve storing capacity

Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans

Co‐evolution of cerebral and cerebellar expansion in cetaceans

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