Abstract
The postnatal development of cerebellar climbing fiber (CF) to Purkinje neuron (PN) synapses is characterized by a substantial pruning during the first 3 weeks after birth, switching from multiple- to single-CF innervation. Previous studies suggested that CF maturation is governed by bidirectional changes of synaptic plasticity. The strengthening of surviving “winner” CFs, which translocate from the PN soma to the dendrite, is thought to be guided by long-term potentiation (LTP), while weakening of to-be-eliminated “loser” CFs, which remain on the soma, was proposed to be due to long-term depression (LTD). However, there are conflicting results from previous studies, whether or not strengthening of winner and weakening of loser CFs during postnatal development is accompanied by changes in short-term plasticity and, thus, whether pre- or postsynaptic forms of LTD and LTP are operational. We, therefore, analyzed the developmental profile of paired-pulse depression (PPD) in “weak” and “strong” CFs in 3–21-day old Igsf9-eGFP mice, which allow visual identification of GFP-labeled CFs. We found that in 3–8-day old mice strong CFs are marked by a stronger PPD compared to weak CFs. Surprisingly, PPD of strong CFs eases during maturation, while PPD in weak CFs remains unchanged. This easing of PPD is neither due to changes in presynaptic influx-release coupling nor to an increased saturation of postsynaptic receptors. Thus, our results imply that synaptic contacts of CFs show distinct features of PPD depending on their affiliation to winner or loser CFs and depending on their somatic or dendritic location.
Highlights
During postnatal maturation of the central nervous system, synaptic contacts face diametrically opposed fates: if they are part of a successfully formed neuronal circuit, they will mature into well-established, strengthened contacts that may persist for the rest of the individual’s life; synaptic contacts not contributing to meaningful neuronal circuits are doomed to become disintegrated or “pruned” within a period of days to weeks
Long-term potentiation (LTP) has been shown to occur at winner synapses only (Bosman et al, 2008; Ohtsuki and Hirano, 2008), either as presynaptic LTP associated with an increase in paired-pulse depression (PPD; Ohtsuki and Hirano, 2008), or, as postsynaptic LTP not associated with alterations in PPD (Bosman et al, 2008)
Our results reveal unexpected developmental differences in short-term plasticity of “weak” and “strong” climbing fiber (CF): (i) in the first postnatal week PPD is stronger in strong CFs compared to weak CFs, (ii) in weak CFs PPD remains stable during the second and third postnatal week, while (iii) strong CFs undergo an easing of PPD during maturation
Summary
During postnatal maturation of the central nervous system, synaptic contacts face diametrically opposed fates: if they are part of a successfully formed neuronal circuit, they will mature into well-established, strengthened contacts that may persist for the rest of the individual’s life; synaptic contacts not contributing to meaningful neuronal circuits are doomed to become disintegrated or “pruned” within a period of days to weeks. In parallel to the maturation of the PN, during which the perisomatic processes are retracted, a single winner CF forms synaptic contacts on the growing main apical dendrite, while all other CFs stay confined to the PN soma and are eliminated (Kano et al, 2018), leading to a CF monoinnervation in at least 98% of the PNs (Eccles et al, 1966). Both processes, the strengthening of winner CFs as well as the elimination of loser CFs, have been linked to long-term plasticity. Our data are in line with the hypothesis that somatic CF contacts undergo presynaptic LTP (Ohtsuki and Hirano, 2008), while CFs that translocated to the PN dendrite may undergo postsynaptic forms of plasticity (Hansel and Linden, 2000; Bosman et al, 2008)
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