Bassoon-disruption slows vesicle replenishment and induces homeostatic plasticity at a CNS synapse

Schulz, Alejandro Mendoza; Jing, Zhizi; Sánchez, J. García; Wetzel, Friederike; Dresbach, Thomas; Strenzke, Nicola; Wichmann, Carolin; Moser, Tobias

doi:10.1002/embj.201385887

Cited by 39 publications

(64 citation statements)

References 85 publications

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“…These results demonstrate that the level of sound evoked activity can dramatically alter the excitability at synapses that relays activity between the auditory nerve and the CN. Pre and post-synaptic homeostatic mechanisms similar to this have also been found to modulate synaptic efficiency and gain in several other forms of cochlear hearing loss (Mendoza Schulz et al, 2014; Oleskevich and Walmsley, 2002; Taberner and Liberman, 2005). …”

Section: Discussionmentioning

confidence: 77%

Plastic changes along auditory pathway during salicylate-induced ototoxicity: Hyperactivity and CF shifts

et al. 2017

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High dose of salicylate, the active ingredient in aspirin, has long been known to induce transient hearing loss, tinnitus and hyperacusis making it a powerful experimental tool. These salicylate-induced perceptual disturbances are associated with a massive reduction in the neural output of the cochlea. Paradoxically, the diminished neural output of the cochlea is accompanied by a dramatic increase in sound-evoked activity in the auditory cortex (AC) and several other parts of the central nervous system. Exactly where the increase in neural activity begins and builds up along the central auditory pathway are not fully understood. To address this issue, we measured sound-evoked neural activity in the cochlea, cochlear nucleus (CN), inferior colliculus (IC), and AC before and after administering a high dose of sodium salicylate (SS, 300 mg/kg). The SS-treatment abolished low-level sound-evoked responses along the auditory pathway resulting in a 20–30 dB threshold shift. While the neural output of the cochlea was substantially reduced at high intensities, the neural responses in the CN were only slightly reduced; those in the IC were nearly normal or slightly enhanced while those in the AC considerably enhanced, indicative of a progress increase in central gain. The SS-induced increase in central response in the IC and AC was frequency-dependent with the greatest increase occurring in the mid-frequency range the putative pitch of SS-induced tinnitus. This frequency-dependent hyperactivity appeared to result from shifts in the frequency receptive fields (FRF) such that the response areas of many FRF shifted/expanded toward the mid-frequencies. Our results suggest that the SS-induced threshold shift originates in the cochlea. In contrast, enhanced central gain is not localized to one region, but progressively builds up at successively higher stage of the auditory pathway either through a loss of inhibition and/or increased excitation.

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Section: Discussionmentioning

confidence: 77%

Plastic changes along auditory pathway during salicylate-induced ototoxicity: Hyperactivity and CF shifts

et al. 2017

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“…Additionally, since the present study focused on the effects of CHL in A1, we cannot exclude whether synaptic scaling or other homeostatic mechanisms take place at lower-order stages of the auditory pathway, which is, however, discussed controversially 16,46 . We found that the suppressive effect of salient sound evoked A1 responses on visually driven V1 activity was precisely restored along with TNFα dependent A1 homeostasis (Fig.…”

Section: Discussionmentioning

confidence: 96%

Homeostatic plasticity and synaptic scaling in the adult mouse auditory cortex

Teichert¹,

Liebmann

Hübner

et al. 2017

Sci Rep

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It has been demonstrated that sensory deprivation results in homeostatic adjustments recovering neuronal activity of the deprived cortex. For example, deprived vision multiplicatively scales up mEPSC amplitudes in the primary visual cortex, commonly referred to as synaptic scaling. However, whether synaptic scaling also occurs in auditory cortex after auditory deprivation remains elusive. Using periodic intrinsic optical imaging in adult mice, we show that conductive hearing loss (CHL), initially led to a reduction of primary auditory cortex (A1) responsiveness to sounds. However, this was followed by a complete recovery of A1 activity evoked sounds above the threshold for bone conduction, 3 days after CHL. Over the same time course patch-clamp experiments in slices revealed that mEPSC amplitudes in A1 layers 2/3 pyramids scaled up multiplicatively in CHL mice. No recovery of sensory evoked A1 activation was evident in TNFα KO animals, which lack synaptic scaling. Additionally, we could show that the suppressive effect of sounds on visually evoked visual cortex activity completely recovered along with TNFα dependent A1 homeostasis in WT animals. This is the first demonstration of homeostatic multiplicative synaptic scaling in the adult A1. These findings suggest that mild hearing loss massively affects auditory processing in adult A1.Homeostatic plasticity is essential in maintaining a stable firing rate in neurons to compensate for prolonged perturbations of neuronal activity 1,2 . For example, a prolonged reduction of neuronal activity of cultured neocortical neurons generated compensatory changes returning firing levels back to control values 1 . Such homeostatic regulations are typically accompanied by an additional insertion of 2-amino-3-(3-hydroxy-5-methyl-isoxasol-4-yl) propanoic acid receptors (AMPARs) into all synapses of a neuron, leading to multiplicatively scaled up mEPSC (miniature excitatory postsynaptic currents) amplitudes or, "synaptic scaling" 2,3 . Specifically, this mechanism is described to globally increase (or decrease) the strength of each synapse of a neuron by the same factor in a multiplicative manner which allows the conservation of information stored in the synaptic weights 4 . Previous studies have demonstrated that synaptic scaling also takes place in vivo, e.g. after reduction of sensory cortex activity due to sensory deprivation. For example, visual deprivation by intraocular TTX injections, dark exposure, binocular enucleation or retinal lesions scales up AMPAR mediated mEPSC amplitudes in layers 2/3 pyramids of the primary visual cortex (V1) in juvenile and adult mice [5][6][7][8][9] . Furthermore, it was shown that prolonged visual deprivation increases visually evoked V1 responses during the visual critical period 10 . However, evidence for homeostatic synaptic scaling in primary auditory cortex and its effects on cortical responsiveness following auditory deprivation is rare.Previously, two models for induction of an auditory deprivation have been used, sensorineural hearing...

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“…; Mendoza Schulz et al . ). We investigated STD in response to AP‐trains applied at 100 Hz (50 stimuli).…”

Section: Resultsmentioning

confidence: 97%

“…; Mendoza Schulz et al . ). We determined the replenishment rate of SVs at the AZ and the RRP size using the cumulative EPSC analysis of 100 Hz AP‐trains.…”

Section: Resultsmentioning

confidence: 97%

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The presynaptic scaffolding protein Piccolo organizes the readily releasable pool at the calyx of Held

Parthier

Kuner

Körber

2018

The Journal of Physiology

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Synaptic vesicles (SVs) are released at the active zone (AZ), a specialized region of the presynaptic plasma membrane organized by a highly interconnected network of multidomain proteins called the cytomatrix of the active zone (CAZ). Two core components of the CAZ are the large, highly homologous scaffolding proteins Bassoon and Piccolo, whose function is not well understood. To investigate their role in synaptic transmission, we established the small hairpin RNA (shRNA)-mediated in vivo knockdown (KD) of Bassoon and Piccolo at the rat calyx of Held synapse. KD of Bassoon and Piccolo, separately or simultaneously, did not affect basic SV release. However, short-term depression (STD) was prominently increased by the KD of Bassoon, whereas KD of Piccolo only had a minor effect. The observed alterations in STD were readily explained by reduced SV replenishment in synapses deficient in either of the proteins. Thus, the regulation of SV refilling during ongoing synaptic activity is a shared function of Bassoon and Piccolo, although Bassoon appears to be more efficient. Moreover, we observed the recruitment of slowly-releasing SVs of the readily-releasable pool (RRP), which are normally not available for action potential-induced release, during high-frequency stimulation in Piccolo-deficient calyces. Therefore, the results obtained in the present study suggest a novel and specific role for Piccolo in the organization of the subpools of the RRP.

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Bassoon-disruption slows vesicle replenishment and induces homeostatic plasticity at a CNS synapse

Cited by 39 publications

References 85 publications

Plastic changes along auditory pathway during salicylate-induced ototoxicity: Hyperactivity and CF shifts

Plastic changes along auditory pathway during salicylate-induced ototoxicity: Hyperactivity and CF shifts

Homeostatic plasticity and synaptic scaling in the adult mouse auditory cortex

The presynaptic scaffolding protein Piccolo organizes the readily releasable pool at the calyx of Held

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