Synaptische und intrinsische Plastizität bei der Kodierung von Stimulus-offsets
Zusammenfassung der Projektergebnisse
Gaps in sound define the space between two words in speech, the rest between two notes in sheet music or even the tiniest temporal differences between two different vowels. Our brain has the ability to recognize and encode these gaps as the silence after a sound is finished via sound-offset responses generated entirely from inhibition. These sound-offset responses are not set in stone but can adapt to changes in the acoustic environment in an experience-dependent manner. Experience-dependent plasticity is the capacity of the brain to wire and rewire itself during early development, but also in response to different experiences made throughout life. In the auditory system, correct wiring results in the ability to detect and respond quickly to changes in the environment, for example the appearance (onset) or disappearance (offset) of an object such as sound. In this project we studied experience-dependent plasticity of those neurons in the brain, that have the ability for de-novo generation of sound-offset responses, the neurons of the superior paraolivary nucleus (SPN). Two main types of changing experience were investigated: changes during postnatal development and changes following acoustic over exposure. In conclusion, the data acquired during this project provide new and crucial information to our understanding of sound-offset responses in the auditory system. We reveal that the main input structure to the SPN and the SPN itself mature early during postnatal development and experience only little further developmental refinement after hearing onset. Our data also show that inhibitory inputs into SPN are significantly larger compared to excitatory inputs at all ages investigated. Interestingly, in SPN neurons, the classical roles for excitation (causing neural firing) and inhibition (modulating neural firing) seem to be switched, with inhibitory inputs now driving action potential firing and excitatory inputs modulating this response. Evidence from in vitro and in vivo recordings suggest that a lack of excitatory inputs to the SPN prolonged offset-response latencies and rendered them more variable to changing sound intensity levels. Our results reveal an unsuspected function for slow excitation in improving the timing of post-inhibitory rebound firing even when paradoxically the firing itself depends entirely on inhibition. Upon a single, two-hour exposure to loud sound, which is very similar to listening to a rock concert, the excitability of SPN neurons was significantly increased leading to higher neural firing rates in the soundoffset response but also in the response to depolarizing stimuli. Interestingly, this experience-dependent increase in excitability was accompanied by an increased strength of the inhibitory inputs which migh serve to neutralize the increase in excitability. In conclusion, the results of our project show that the auditory system employs highly specialized mechanisms to encode timing-sensitive features of sound offsets which are crucial in perception of sound duration, detection of brief gaps in noise, and discrimination of temporally discontinuous communication sounds such as speech.
Projektbezogene Publikationen (Auswahl)
- (2014) Nitric oxide signaling modulates synaptic inhibition in the superior paraolivary nucleus (SPN) via cGMP-dependent suppression of KCC2. Front Neural Circuits 8:65
Yassin L, Radtke-Schuller S, Asraf H, Grothe B, Hershfinkel M, Forsythe ID, Kopp-Scheinpflug C
(Siehe online unter https://doi.org/10.3389/fncir.2014.00065) - (2015) Nitric oxide selectively suppresses IH currents mediated by HCN1-containing channels. J Physiol 593:1685-1700
Kopp-Scheinpflug C, Pigott BM, Forsythe ID
(Siehe online unter https://doi.org/10.1113/jphysiol.2014.282194) - (2016) Physiology and anatomy of neurons in the medial superior olive of the mouse. J Neurophysiol 116:2676-2688
Fischl MJ, Burger RM, Schmidt-Pauly M, Alexandrova O, Sinclair JL, Grothe B, Forsythe ID, Kopp- Scheinpflug C
(Siehe online unter https://doi.org/10.1152/jn.00523.2016) - (2017) Sound-Evoked Activity Influences Myelination of Brainstem Axons in the Trapezoid Body. J Neurosci 37:8239-8255
Sinclair JL, Fischl MJ, Alexandrova O, Heß M, Grothe B, Leibold C, Kopp-Scheinpflug C
(Siehe online unter https://doi.org/10.1523/JNEUROSCI.3728-16.2017) - (2018) Integration of Synaptic and Intrinsic Conductances Shapes Microcircuits in the Superior Olivary Complex. In: The Mammalian Auditory Pathways: Synaptic Organization and Microcircuits (Oliver DL, Cant NB, Fay RR, Popper AN, eds), pp 101-126. Cambridge Springer International Publishing
Kopp-Scheinpflug C, Forsythe ID
(Siehe online unter https://doi.org/10.1007/978-3-319-71798-2_5) - (2018) When Sound Stops: Offset Responses in the Auditory System. Trends Neurosci 41:712-728
Kopp-Scheinpflug C, Sinclair JL, Linden JF
(Siehe online unter https://doi.org/10.1016/j.tins.2018.08.009)
