bims-climfi 2021-07-04 papers

Issue of 2021–07–04
two papers selected by
Jun Maruta, Mount Sinai Health System

Mol Cell Neurosci. 2021 Jun 28. pii: S1044-7431(21)00063-4. [Epub ahead of print] 103650

Parvalbumin subtypes of cerebellar Purkinje cells contribute to differential intrinsic firing properties.

Cheryl Brandenburg, Lindsey A Smith, Michaela B C Kilander, Morgan S Bridi, Yu-Chih Lin, Shiyong Huang, Gene J Blatt.

Purkinje cells (PCs) are central to cerebellar information coding and appreciation for the diversity of their firing patterns and molecular profiles is growing. Heterogeneous subpopulations of PCs have been identified that display differences in intrinsic firing properties without clear mechanistic insight into what underlies the divergence in firing parameters. Although long used as a general PC marker, we report that the calcium binding protein parvalbumin labels a subpopulation of PCs, based on high and low expression, with a conserved distribution pattern across the animals examined. We trained a convolutional neural network to recognize the parvalbumin subtypes and create maps of whole cerebellar distribution and find that PCs within these areas have differences in spontaneous firing that can be modified by altering calcium buffer content. These subtypes also show differential responses to potassium and calcium channel blockade, suggesting a mechanistic role for variability in PC intrinsic firing through differences in ion channel composition. It is proposed that ion channels drive the diversity in PC intrinsic firing phenotype and parvalbumin calcium buffering provides capacity for the highest firing rates observed. These findings open new avenues for detailed classification of PC subtypes.

Keywords: Burst-pause; Calcium homeostasis; Intrinsic plasticity; Parvalbumin; Purkinje; Spontaneous firing

DOI: https://doi.org/10.1016/j.mcn.2021.103650

Front Neural Circuits. 2021 ;15 661899

Modulatory Effects of Monoamines and Perineuronal Nets on Output of Cerebellar Purkinje Cells.

Moritoshi Hirono, Fuyuki Karube, Yuchio Yanagawa.

Classically, the cerebellum has been thought to play a significant role in motor coordination. However, a growing body of evidence for novel neural connections between the cerebellum and various brain regions indicates that the cerebellum also contributes to other brain functions implicated in reward, language, and social behavior. Cerebellar Purkinje cells (PCs) make inhibitory GABAergic synapses with their target neurons: other PCs and Lugaro/globular cells via PC axon collaterals, and neurons in the deep cerebellar nuclei (DCN) via PC primary axons. PC-Lugaro/globular cell connections form a cerebellar cortical microcircuit, which is driven by serotonin and noradrenaline. PCs' primary outputs control not only firing but also synaptic plasticity of DCN neurons following the integration of excitatory and inhibitory inputs in the cerebellar cortex. Thus, strong PC-mediated inhibition is involved in cerebellar functions as a key regulator of cerebellar neural networks. In this review, we focus on physiological characteristics of GABAergic transmission from PCs. First, we introduce monoaminergic modulation of GABAergic transmission at synapses of PC-Lugaro/globular cell as well as PC-large glutamatergic DCN neuron, and a Lugaro/globular cell-incorporated microcircuit. Second, we review the physiological roles of perineuronal nets (PNNs), which are organized components of the extracellular matrix and enwrap the cell bodies and proximal processes, in GABA release from PCs to large glutamatergic DCN neurons and in cerebellar motor learning. Recent evidence suggests that alterations in PNN density in the DCN can regulate cerebellar functions.

Keywords: Deep cerebellar nuclei; Lugaro cell; axon collateral; chondroitinase ABC; eyeblink conditioning; globular cell; noradrenaline; serotoinin

DOI: https://doi.org/10.3389/fncir.2021.661899