Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB293

Poster Communications

Developmental easing of short-term depression in ‘winner' climbing fibers

C. Paetz1, S. Brachtendorf1, J. Eilers1

1. 2, Carl-Ludwig-Insitute for Physiology, Leipzig, Germany.

Cerebellar climbing fibers (CFs) undergo a substantial pruning during the first three postnatal weeks. As a result, the innervation of Purkinje cells, their main targets in the cerebellum, switches from multiple- to single-CF innervation. The associated strengthening of the remaining ‘winner' CF is thought to be guided by long-term potentiation (LTP) (1, 2). In contrast, ‘looser' CFs were proposed to be weakened by presynaptic long-term depression (LTD), ultimately leading to their elimination (2). It remained unclear whether LTP of winner CFs is pre- (2) or postsynaptically (1) expressed and whether corresponding changes in paired-pulse depression (PPD) occur in the pruning period: an increase of PPD would accompany presynaptic LTP, while postsynaptic LTP would not affect PPD. We, therefore, analyzed the developmental profile of CF-PPD in the first three weeks after birth [postnatal (p) day 3-21], dividing the animals into three age groups p3-p8, p9-p12, and p13-p21. Igsf9-eGFP mice, which allow visually-guided stimulation of GFP-labeled CFs (3), were anesthetized by inhalation of isoflurane. Slice preparation and paired-pulse experiments were performed as described previously (3). Excitatory postsynaptic currents (EPSCs) evoked by CFs were classified as originating from winner CFs when their peak amplitude exceeded -360 pA (at a holding potential of -75 mV) or from looser CFs otherwise. We found a developmental easing of PPD in winner but no change in looser CFs. Winner CFs showed PPD values of 0.15±0.017 at p3-p8 (n=12), 0.19±0.012 at p9-p12 (n=40), and 0.33±0.023 at P13-p21 (n=46), the latter reaching statistical significance compared to both other age groups (p<0.05, Dunn-Holland-Wolfe test). The easing was well described by a Hill equation with start and end PPD values of 0.14 and 0.43, respectively, the inflexion point at p13 and a Hill coefficient of 5.36. Looser CFs, which were only found at sufficient numbers up to p12, showed PPD values of 0.23±0.032 at p3-p8 (n=15) and 0.21±0.017 at p9-p12 (n=19). Taken together, our data unexpectedly reveal that maturation of winner CFs is associated with an easing of PPD, denoting a decrease in the release probability and that PPD in looser CFs remains unchanged. Thus, neither pre- nor postsynaptic LTP appears to persistently contribute to the maturation of winner CFs, nor presynaptic LTD to elimination of looser CFs. We propose a simpler scenario in which synapses on dendrites (harboring the growing winner CF) and somata (harboring looser CFs and to-be-disintegrated synaptic contacts of the winner CF) are characterized by different release probabilities.

Where applicable, experiments conform with Society ethical requirements