Calcium dynamics and regulation in horizontal cells of the vertebrate retina: lessons from teleosts

Abstract

Horizontal cells (HCs) are inhibitory interneurons of the vertebrate retina. Unlike typical neurons, HCs are chronically depolarized in the dark, leading to a constant influx of Ca Therefore, mechanisms of Ca homeostasis in HCs must differ from neurons elsewhere in the central nervous system, which undergo excitotoxicity when they are chronically depolarized or stressed with Ca HCs are especially well characterized in teleost fish and have been used to unlock mysteries of the vertebrate retina for over one century. More recently, mammalian models of the retina have been increasingly informative for HC physiology. We draw from both teleost and mammalian models in this review, using a comparative approach to examine what is known about Ca pathways in vertebrate HCs. We begin with a survey of Ca-permeable ion channels, exchangers, and pumps and summarize Ca influx and efflux pathways, buffering, and intracellular stores. This includes evidence for Ca-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and N-methyl-d-aspartate receptors and for voltage-gated Ca channels. Special attention is given to interactions between ion channels, to differences among species, and in which subtypes of HCs these channels have been found. We then discuss a number of unresolved issues pertaining to Ca dynamics in HCs, including a potential role for Ca in feedback to photoreceptors, the role for Ca-induced Ca release, and the properties and functions of Ca-based action potentials. This review aims to highlight the unique Ca dynamics in HCs, as these are inextricably tied to retinal function.

Rapid 3D Enhanced Resolution Microscopy Reveals Diversity in Dendritic Spinule Dynamics, Regulation, and Function

“…These findings are consistent with previous reports of their induction by various types of stimulation; i.e., estradiol (Murphy and Andrews, 2000), high K + depolarization (Tao-Cheng et al, 2009), cLTP (Stewart et al, 2005), high-frequency stimulation (Toni et al, 2001), glutamate application (Richards et al, 2005), and glutamate uncaging (Ueda and Hayashi, 2013). EM studies suggest that spinules in the teleost retina form in response to Ca 2+ -dependent synaptic plasticity (Country and Jonz, 2017). We found that Ca 2+ is crucial for mammalian spinule formation and observed Ca 2+ nanodomains within spinules isolated from but often in synchrony with spine heads.…”

“…Spinules can be induced by neuronal depolarization and Nmethyl-D-aspartate (NMDA) treatment (Tao-Cheng et al, 2009) as well as theta burst stimulation and glutamate application (Ueda and Hayashi, 2013). Although studies show that Ca 2+ , a key signaling ion in synaptic transmission, regulates spinuledependent synaptic plasticity in fish horizontal cells (Country and Jonz, 2017), the role of Ca 2+ in mammalian spinule regulation remains unclear. Actin regulatory pathways may be involved in spinule development (Colicos et al, 2001), and PIP 3 has been shown to regulate spinules during structural long-term potentiation (sLTP) (Ueda and Hayashi, 2013).…”

Rapid 3D enhanced resolution microscopy reveals the dynamics of cortical dendritic spinules

“…In accordance with rapid SIM, a significant positive correlation was found between mean spinule length and lifespan, and both the mean and maximum spinule length was substantially higher in long-as opposed to short-lived spinules ( Figure S3C-D). Short-lived spinules typically originated near to the PSD edge, while long-lived spinules originated substantially further from the edge of more complex PSDs, at a mean distance of 0.28 and 0.43 µm, respectively ( Figure 3B Ca 2+ is a key signaling ion in synaptic transmission, which induces spinule formation (Petralia et al, 2015, Tao-Cheng et al, 2009, Ueda and Hayashi, 2013, and regulates spinuledependent synaptic plasticity in the retina of teleosts (Country and Jonz, 2017). To investigate Ca 2+ as a candidate regulator of mammalian spinules during basal activity, we again utilized fast (2.2 sec/frame) enhanced resolution confocal imaging of neurons expressing the Ca 2+ sensor GCaMP6s (Chen et al, 2013).…”

“…Moreover, Ca 2+ is a key signaling ion in a multitude of synaptic functions, including synaptic transmission, which is known to induce spinule formation (Petralia et al, 2015, Tao-Cheng et al, 2009, Ueda and Hayashi, 2013. Ca 2+ regulates spinule-dependent synaptic plasticity in fish horizontal cells (Country and Jonz, 2017), but the role of Ca 2+ in mammalian spinule formation remains unclear, necessitating live, high-speed imaging studies.…”

Seasonal changes in membrane structure and excitability in central neurons of goldfish (Carassius auratus) under constant environmental conditions

“…Moreover, the unstimulated retina generally has high energy requirements due to photoreceptor dark current and high Na + /K + -ATPase activity (Ames, 1992;Country, 2017). Horizontal cells receive tonic stimulation from photoreceptors yet actively maintain transmembrane ionic gradients, regulate intracellular Ca 2+ homeostasis and (in fish) support loading of synaptic vesicles with γ-aminobutyric acid (GABA) for Ca 2+ -dependent neurosecretion (Thoreson and Mangel, 2012;Country and Jonz, 2017)-all of which are mechanisms that consume energy in the form of ATP. Reduced activity in horizontal cells during the winter may, therefore, lower energy consumption in cold-and anoxia-tolerant animals, such as goldfish.…”