Functional Properties of Dendritic Gap Junctions in Cerebellar Golgi Cells

Abstract

SummaryThe strength and variability of electrical synaptic connections between GABAergic interneurons are key determinants of spike synchrony within neuronal networks. However, little is known about how electrical coupling strength is determined due to the inaccessibility of gap junctions on the dendritic tree. We investigated the properties of gap junctions in cerebellar interneurons by combining paired somato-somatic and somato-dendritic recordings, anatomical reconstructions, immunohistochemistry, electron microscopy, and modeling. By fitting detailed compartmental models of Golgi cells to their somato-dendritic voltage responses, we determined their passive electrical properties and the mean gap junction conductance (0.9 nS). Connexin36 immunofluorescence and freeze-fracture replica immunogold labeling revealed a large variability in gap junction size and that only 18% of the 340 channels are open in each plaque. Our results establish that the number of gap junctions per connection is the main determinant of both the strength and variability in electrical coupling between Golgi cells.

Unique membrane properties and enhanced signal processing in human neocortical neurons

“…We obtained an experimental value for C m of 0.51 ± 0.11 μF/cm 2 (mean ± S.D, n = 5 neurons, see details on these cells in Table 2), in full agreement with our model prediction (Figure 2). Repeating the same procedure in mouse neurons resulted in a C m of 0.83 ± 0.34 μF/cm 2  (n = 7 neurons from 7 mice; Figure 2d), similar to the findings of (Gentet et al, 2000; Szoboszlay et al, 2016) and significantly different from the human C m values (students t-test following the KS test for normality (Massey, 1951), p-val = 0.0472). Combining the C m values obtained in both methods, the model fittings (Figure 1) and the nucleated patches (Figure 2) shows the large difference in C m between human ( C m  = 0.49 ± 0.08 μF/cm 2 , n = 11) and mouse ( C m  = 0.93 ± 0.36 μF/cm 2 , n = 11).…”

“…The low C m value ~ 0.5 μF/cm 2 found in HL2/3 PCs is surprising; it is commonly assumed that C m is close to 1 μF/cm 2 (Hodgkin et al, 1952; Cole, 1968), as was modeled by many researchers on rodent neurons (Major et al, 1994; Roth and Häusser, 2001; Nörenberg et al, 2010; Szoboszlay et al, 2016) and directly confirmed for several classes of neurons using patch recordings from nucleated membrane patches (Gentet et al, 2000). For self-consistency, we repeated the same experimental and theoretical protocols as in Figure 1 on L2/3 PCs from the mouse temporal cortex (n = 4).…”

“…In particular, we showed that layer 2/3 pyramidal neurons from human temporal cortex have a specific membrane capacitance ( C m ) of ~0.5 µF/cm 2 , half of the commonly accepted ‘universal’ value (~1 µF/cm 2 ) for biological membranes. It is important to note that a few studies have demonstrated that C m in rodent’s pyramidal neurons may range between 0.7–2 µF/cm 2 (Major et al, 1994; Thurbon et al, 1998), but direct measurements using nucleated patches found a much narrower range, 0.8–1.1 µF/cm 2 , in cortical pyramidal neurons (Gentet et al, 2000; Szoboszlay et al, 2016), as well as in cerebellar Golgi cells (Szoboszlay et al, 2016). This narrow range of values also agrees with the modeling prediction of (Nörenberg et al, 2010) for GABAergic hippocampal interneurons, where a correction for the spines area is not required.…”

The conception of the reticular organization of the nervous tissue of Alexander Dogiel

“…Он не мог предположить, что морфологами будут описаны щелевые контакты [21,45,46], а физиологами будет обнаружена возможность их двухсторонней электрической взаимосвязи нервных отростков, как предполагали ретикуляристы [47][48][49], нельзя было предвидеть и существование механизмов смешанных, электро-медиаторных синапсов [25,49]. Ставя в заглавие своего последнего теоретического трактата «Нейрональная теория или ретикулярная теория?» вопросительный знак, он привел огромное число фактов, бесспорно свидетельствующих о реальности синаптической связи нейронов, но в заключительных фразах Кахаль уже не возражал против существования и межнейронных анастомозов, то есть явлений, подтверждающих ретикуляризм.…”

Gap Junction Modulation of Low-Frequency Oscillations in the Cerebellar Granule Cell Layer

“…Electrical coupling effects within the GCL between Golgi cells were recently identified [18,32,33], indicating a possible mechanism by which changes in membrane potential of Golgi cells may spread quickly across the layer, and promote synchronization of the GCL network. The strength of connectivity between Golgi cells is determined by the number of open gap junctions [34]. In in vitro recordings between Golgi cells, gap junctions were shown to facilitate the rapid spread of activity within the GCL, and thus promote synchronous firing and widespread synchronous inhibition of granule cells [18,32].…”