Parasagittally aligned, mGluR₁-dependent patches are evoked at long latencies by parallel fiber stimulation in the mouse cerebellar cortex in vivo

Abstract

Wang X, Chen G, Gao W, Ebner TJ. Parasagittally aligned, mGluR 1 -dependent patches are evoked at long latencies by parallel fiber stimulation in the mouse cerebellar cortex in vivo. J Neurophysiol 105: 1732-1746, 2011. First published February 2, 2011 doi:10.1152/jn.00717.2010.-The parallel fibers (PFs) in the cerebellar cortex extend several millimeters along a folium in the mediolateral direction. The PFs are orthogonal to and cross several parasagittal zones defined by the olivocerebellar and corticonuclear pathways and the expression of molecular markers on Purkinje cells (PCs). The functions of these two organizations remain unclear, including whether the bands respond similarly or differentially to PF input. By using flavoprotein imaging in the anesthetized mouse in vivo, this study demonstrates that high-frequency PF stimulation, which activates a beamlike response at short latency, also evokes patches of activation at long latencies. These patches consist of increased fluorescence along the beam at latencies of 20 -25 s with peak activation at 35 s. The long-latency patches are completely blocked by the type 1 metabotropic glutamate receptor (mGluR 1 ) antagonist LY367385. Conversely, the AMPA and NMDA glutamate receptor antagonists DNQX and APV have little effect. Organized in parasagittal bands, the long-latency patches align with zebrin II-positive PC stripes. Additional Ca 2ϩ imaging demonstrates that the patches reflect increases in intracellular Ca 2ϩ . Both the PLC␤ inhibitor U73122 and the ryanodine receptor inhibitor ryanodine completely block the long-latency patches, indicating that the patches are due to Ca 2ϩ release from intracellular stores. Robust, mGluR 1 -dependent longterm potentiation (LTP) of the patches is induced using a highfrequency PF stimulation conditioning paradigm that generates LTP of PF-PC synapses. Therefore, the parasagittal bands, as defined by the molecular compartmentalization of PCs, respond differentially to PF inputs via mGluR 1 -mediated release of internal Ca 2ϩ .

Differential Purkinje cell simple spike activity and pausing behavior related to cerebellar modules

“…Although intensively studied, previous work has focused on the charaterization and possible role of SS pauses, with limited interest in the cerebellar cortical location of the studied PCs (Kim et al 2012;Sugihara and Quy 2007;Wadiche and Jahr 2005;Wang et al 2011;Xiao et al 2014;Zhou et al 2014). In the current study, we systemically correlated the locations of PCs with the occurrence of long pauses and found that these cells are often located close to the exposed brain surface, near the craniotomy.…”

“…PCs that have a similar zebrin "identity," i.e., have a similar expression level of zebrin II (from here on: zebrin), typically receive inputs from the same part of the inferior olive, and project their axons to the same part of the cerebellar nuclei (Apps and Hawkes 2009;Brochu et al 1990;Pijpers et al 2006;Sugihara 2011;Sugihara and Quy 2007;Voogd and Ruigrok 2004), creating functional units, or modules. More recently physiological differences between modules have been described in terms of plasticity (Wadiche and Jahr 2005;Wang et al 2011) and firing dynamics and rates (Kim et al 2012;Xiao et al 2014;Zhou et al 2014). In addition, the cerebellar cortex can also be subdivided in zones on the basis of development and function by borders that run perpendicular to the sagittal bands, i.e., into transverse zones (Ozol et al 1999;Reeber et al 2013).…”

Structure–Function Relationships between Aldolase C/Zebrin II Expression and Complex Spike Synchrony in the Cerebellum

“…Although the function of aldolase C/zebrin II in the cerebellum is still largely unclear, other physiologically important molecules (e.g., mGluR1b, phospholipase C␤3/4, protein kinase C␦, and glutamate transporter EAAT4) in PCs are known to exhibit the same or complementary stripe-shaped expression patterns as aldolase C (Chen and Hillman, 1993;Sarna et al, 2006;Paukert et al, 2010;Wang et al, 2011). Thus aldolase C compartmentalization is of the same functional importance as above molecules in the cerebellar cortex.…”

“…Thus aldolase C compartmentalization is of the same functional importance as above molecules in the cerebellar cortex. Indeed, a recent study has shown that firing properties of PCs depend on the expression of aldolase C (Zhou et al, 2014). These previous studies required post hoc anatomical identification of aldolase C compartments in perfused brain sections.…”

“…It is therefore possible that electrotonic coupling between neuronal ensembles in the inferior olive are modulated by inputs from the cerebral cortex depending on vigilance or behavioral state of the animal. Presumed weak coupling between tightly coupled cell assemblies might be enhanced, leading to the elevation of synchrony between these assemblies (De Zeeuw et al, 2011). Coactivation of neighboring microzones implies the facilitation of coupling between microzones with different (e.g., sensory and motor) modalities under awake conditions.…”