bims-climfi 2019-05-26 papers

Issue of 2019‒05‒26
three papers selected by
Jun Maruta
Mount Sinai Health System

Front Cell Neurosci. 2019 ;13 183

Developmental Easing of Short-Term Depression in "Winner" Climbing Fibers.

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.

Keywords: Purkinje neuron; cerebellum; climbing fibers; paired-pulse depression; short-term plasticity

DOI: https://doi.org/10.3389/fncel.2019.00183

Pflugers Arch. 2019 May 19.

Plasticity leading to cerebellum-dependent learning: two different regions, two different types.

Jang DC, Kim SJ.

In memory research, studying cerebellum-dependent memory is advantageous due to its relatively simple neural architecture compared with that of other memory circuits. To understand how cerebellum-dependent memory develops and is stored in this circuit, numerous hypotheses have been proposed. These hypotheses are generally able to adequately explain most learning and memory processes; however, several reported results are still poorly understood. Recently, the importance of intrinsic plasticity (i.e., plasticity of intrinsic excitability) has been highlighted in several studies. Because the classical view of cerebellum-dependent eye movement learning was focused on synaptic plasticity, it is valuable to consider the intrinsic plasticity for deeper understanding. In the present review, we re-examine the utility and limitations of previous hypotheses, from classic to recent, and propose an updated hypothesis. Integrating intrinsic plasticity into current models of the vestibulo-ocular reflex (VOR) circuit may facilitate deeper understanding of the VOR adaptation process. In particular, during the period of memory transfer, dynamic changes in excitability in both cerebellar Purkinje cells and vestibular nuclear neurons illuminate the role of intrinsic plasticity in the circuit.

Keywords: Cerebellum; Intrinsic plasticity; Memory; Purkinje cells; Vestibular nucleus; Vestibulo-ocular reflex (VOR)

DOI: https://doi.org/10.1007/s00424-019-02282-3

eNeuro. 2019 May 20. pii: ENEURO.0126-19.2019. [Epub ahead of print]

Cerebellar stellate cell excitability is coordinated by shifts in the gating behavior of voltage-gated Na+ and A-type K+ channels.

Alexander RPD, Mitry J, Sareen V, Khadra A, Bowie D.

Neuronal excitability in the vertebrate brain is governed by the coordinated activity of both ligand- and voltage-gated ion channels. In the cerebellum, spontaneous action potential (AP) firing of inhibitory stellate cells (SCs) is variable, typically operating within the 5-30 Hz frequency range. AP frequency is shaped by the activity of somatodendritic A-type K+ channels and the inhibitory effect of GABAergic transmission. An added complication, however, is that whole-cell recording from SCs induces a time-dependent and sustained increase in membrane excitability making it difficult to define the full range of firing rates. Here, we show that whole-cell recording in cerebellar SCs of both male and female mice augments firing rates by reducing the membrane potential at which APs are initiated. AP threshold is lowered due to a hyperpolarizing shift in the gating behavior of voltage-gated Na+ channels. Whole-cell recording also elicits a hyperpolarizing shift in the gating behavior of A-type K+ channels which contributes to increased firing rates. Hodgkin-Huxley modeling and pharmacological experiments reveal that gating shifts in A-type K+ channel activity do not impact AP threshold, but rather promote channel inactivation which removes restraint on the upper limit of firing rates. Taken together, our work reveals an unappreciated impact of voltage-gated Na+ channels that work in coordination with A-type K+ channels to regulate the firing frequency of cerebellar SCs.Significance Statement The cerebellum is a brain region that fulfills critical roles in motor function in adults as well as being linked to neurodevelopmental disorders in the developing brain. Significant attention has been directed towards understanding connectivity within the cerebellum and how its neuronal circuits are regulated. Stellate cells are inhibitory GABAergic interneurons that make-up neuronal circuits that control the output from the cerebral cortex by regulating the firing properties of Purkinje cells. The strength of GABAergic inhibition of Purkinje cells is governed by the excitability of stellate cells which fire action potentials at a wide range of frequencies. Our study reveals an unappreciated role of voltage-gated sodium channels that work in coordination with A-type K+-channels to establish stellate cell firing rates.

Keywords: A-type potassium channe; action potential; cerebellum; computational modelling; sodium channel; stellate cell

DOI: https://doi.org/10.1523/ENEURO.0126-19.2019