Electrical Synapses Research Articles

Burst mechanisms and burst synchronization in a system of coupled type-I and type-II neurons

The rich dynamics of a system comprising of a Type-I neuron coupled to a Type-II neuron via an electrical synapse (gap junction) are explored in this paper. Diverse dynamical behaviour ranging from quiescence and periodic spiking, to bursting and burst synchronization, were observed for different coupling schemes. The bifurcation mechanisms underlying the various bursts observed were identified. We report a unique burst mechanism, based on a focus/node bifurcation, occurring for bidirectionally coupled neurons. We attempt to understand the physical basis for the transitions from one burst pattern to another and also between the different aforementioned forms of dynamical behaviour observed on varying the coupling strength, in both unidirectionally and bidirectionally coupled neurons. The various dynamical regimes of the coupled system are exhaustively studied and demarcated through parameter plots. Type-I and type-II neurons exhibit mutually phase synchronized burst patterns at large values of the coupling which tend towards complete synchronization on increasing the coupling strength. Such collective dynamical behaviour can have important implications in biological systems.

Dopamine Improves Resistance of Dendrites of Mauthner Neurons to Destruction Induced by Sensory Stimulation and Application of Β-Amyloid.

Mauthner neurons in goldfish fry were studied by the methods of light and electron microscopy. The structure and volume of individual dendrites as well as the structure of axodendritic synapses were examined using virtual images of neurons formed from serial 3-μ sections. In short-time (5 h) experiments with application of dopamine, β-amyloid fragment (25-35), and long-term sensory stimulation affecting afferent inputs to Mauthner neurons, the dendrites were larger than the same dendrites under the same conditions without dopamine application. Application of dopamine induced no pathological changes in the structure of axodendritic chemical and electric synapses containing desmosome-like contacts.

Neuronal Glutamatergic Network Electrically Wired with Silent But Activatable Gap Junctions.

It is widely assumed that electrical synapses in the mammalian brain, especially between interneurons, underlie neuronal synchrony. In the hippocampus, principal cells also establish electrical synapses with each other and have also been implicated in network oscillations, whereby the origin of fast electrical activity has been attributed to ectopic spikelets and dendro-dendritic or axo-axonal gap junctions. However, if electrical synapses were in axo-dendritic connections, where chemical synapses occur, the synaptic events would be mixed, having an electrical component preceding the chemical one. This type of communication is less well studied, mainly because it is not easily detected. Moreover, a possible scenario could be that an electrical synapse coexisted with a chemical one, but in a nonconductive state; hence, it would be considered inexistent. Could chemical synapses have a quiescent electrical component? If so, can silent electrical synapses be activated to be detected? We addressed this possibility, and we here report that, indeed, the connexin-36-containing glutamatergic mossy fiber synapses of the rat hippocampus express previously unrecognized electrical synapses, which are normally silent. We reveal that these synapses are pH sensitive, actuate in vitro and in vivo, and that the electrical signaling is bidirectional. With the simultaneous recording of hundreds of cells, we could reveal the existence of an electrical circuit in the hippocampus of adult rats of either sex consisting of principal cells where the nodes are interregional glutamatergic synapses containing silent but ready-to-use gap junctions.SIGNIFICANCE STATEMENT In this work, we present a series of experiments, both in vitro and in vivo, that reveal previously unrecognized silent pH-sensitive electrical synapses coexisting in one of the best studied glutamatergic synapses of the brain, the mossy fiber synapse of the hippocampus. This type of connectivity underlies an "electrical circuit" between two substructures of the adult rat hippocampus consisting of principal cells where the nodes are glutamatergic synapses containing silent but ready-to-use gap junctions. Its identification will allow us to explore the participation of such a circuit in physiological and pathophysiological functions and will provide valuable conceptual tools to understanding computational and regulatory mechanisms that may underlie network activity.

Differential Contribution of Gap Junctions to the Membrane Properties of ON- and OFF-Bipolar Cells of the Rat Retina

Gap junctions are ubiquitous within the retina, but in general, it remains to be determined whether gap junction coupling between specific cell types is sufficiently strong to mediate functionally relevant coupling via electrical synapses. From ultrastructural, tracer coupling and immunolabeling studies, there is clear evidence for gap junctions between cone bipolar cells, but it is not known if these gap junctions function as electrical synapses. Here, using whole-cell voltage-clamp recording in rat (male and female) retinal slices, we investigated whether the gap junctions of bipolar cells make a measurable contribution to the membrane properties of these cells. We measured the input resistance (RN) of bipolar cells before and after applying meclofenamic acid (MFA) to block gap junctions. In the presence of MFA, RN of ON-cone bipolar cells displayed a clear increase, paralleled by block of the electrical coupling between these cells and AII amacrine cells in recordings of coupled cell pairs. For OFF-cone and rod bipolar cells, RN did not increase in the presence of MFA. The results for rod bipolar cells are consistent with the lack of gap junctions in these cells. However, for OFF-cone bipolar cells, our results suggest that the morphologically identified gap junctions between these cells do not support a junctional conductance that is sufficient to mediate effective electrical coupling. Instead, these junctions might play a role in chemical and/or metabolic coupling between subcellular compartments.

Understanding the Molecular and Cell Biological Mechanisms of Electrical Synapse Formation

In this review article, we will describe the recent advances made towards understanding the molecular and cell biological mechanisms of electrical synapse formation. New evidence indicates that electrical synapses, which are gap junctions between neurons, can have complex molecular compositions including protein asymmetries across joined cells, diverse morphological arrangements, and overlooked similarities with other junctions, all of which indicate new potential roles in neurodevelopmental disease. Aquatic organisms, and in particular the vertebrate zebrafish, have proven to be excellent models for elucidating the molecular mechanisms of electrical synapse formation. Zebrafish will serve as our main exemplar throughout this review and will be compared with other model organisms. We highlight the known cell biological processes that build neuronal gap junctions and compare these with the assemblies of adherens junctions, tight junctions, non-neuronal gap junctions, and chemical synapses to explore the unknown frontiers remaining in our understanding of the critical and ubiquitous electrical synapse.

Melanopsin Driven Light Responses Across a Large Fraction of Retinal Ganglion Cells in a Dystrophic Retina.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and project to central targets, allowing them to contribute to both image-forming and non-image forming vision. Recent studies have highlighted chemical and electrical synapses between ipRGCs and neurons of the inner retina, suggesting a potential influence from the melanopsin-born signal to affect visual processing at an early stage of the visual pathway. We investigated melanopsin responses in ganglion cell layer (GCL) neurons of both intact and dystrophic mouse retinas using 256 channel multi-electrode array (MEA) recordings. A wide 200 μm inter-electrode spacing enabled a pan-retinal visualization of melanopsin’s influence upon GCL activity. Upon initial stimulation of dystrophic retinas with a long, bright light pulse, over 37% of units responded with an increase in firing (a far greater fraction than can be expected from the anatomically characterized number of ipRGCs). This relatively widespread response dissipated with repeated stimulation even at a quite long inter-stimulus interval (ISI; 120 s), to leave a smaller fraction of responsive units (<10%; more in tune with the predicted number of ipRGCs). Visually intact retinas appeared to lack such widespread melanopsin responses indicating that it is a feature of dystrophy. Taken together, our data reveal the potential for anomalously widespread melanopsin responses in advanced retinal degeneration. These could be used to probe the functional reorganization of retinal circuits in degeneration and should be taken into account when using retinally degenerate mice as a model of disease.

In silico analyses suggest the cardiac ganglion of the lobster, Homarus americanus, contains a diverse array of putative innexin/innexin-like proteins, including both known and novel members of this protein family.

Gap junctions are physical channels that connect adjacent cells, permitting the flow of small molecules/ions between the cytoplasms of the coupled units. Innexin/innexin-like proteins are responsible for the formation of invertebrate gap junctions. Within the nervous system, gap junctions often function as electrical synapses, providing a means for coordinating activity among electrically coupled neurons. While some gap junctions allow the bidirectional flow of small molecules/ions between coupled cells, others permit flow in one direction only or preferentially. The complement of innexins present in a gap junction determines its specific properties. Thus, understanding innexin diversity is key for understanding the full potential of electrical coupling in a species/system. The decapod crustacean cardiac ganglion (CG), which controls cardiac muscle contractions, is a simple pattern-generating neural network with extensive electrical coupling among its circuit elements. In the lobster, Homarus americanus, prior work suggested that the adult neuronal innexin complement consists of six innexins (Homam-Inx1-4 and Homam-Inx6-7). Here, using a H. americanus CG-specific transcriptome, we explored innexin complement in this portion of the lobster nervous system. With the exception of Homam-Inx4, all of the previously described innexins appear to be expressed in the H. americanus CG. In addition, transcripts encoding seven novel putative innexins (Homam-Inx8-14) were identified, four (Homam-Inx8-11) having multiple splice variants, e.g., six for Homam-Inx8. Collectively, these data indicate that the innexin complement of the lobster nervous system in general, and the CG specifically, is likely significantly greater than previously reported, suggesting the possibility of expanded gap junction diversity and function in H. americanus.

Localized Calcium Signaling and the Control of Coupling at Cx36 Gap Junctions.

A variety of electrical synapses are capable of activity-dependent plasticity, including both activity-dependent potentiation and activity-dependent depression. In several types of neurons, activity-dependent electrical synapse plasticity depends on changes in the local Ca2+ environment. To enable study of local Ca2+ signaling that regulates plasticity, we developed a GCaMP Ca2+ biosensor fused to the electrical synapse protein Connexin 36 (Cx36). Cx36-GCaMP transfected into mammalian cell cultures formed gap junctions at cell-cell boundaries and supported Neurobiotin tracer coupling that was regulated by protein kinase A signaling in the same way as Cx36. Cx36-GCaMP gap junctions robustly reported local Ca2+ increases in response to addition of a Ca2+ ionophore with increases in fluorescence that recovered during washout. Recovery was strongly dependent on Na+-Ca2+ exchange activity. In cells transfected with NMDA receptor subunits, Cx36-GCaMP revealed transient and concentration-dependent increases in local Ca2+ on brief application of glutamate. In HeLa cells, glutamate application increased Cx36-GCaMP tracer coupling through a mechanism that depended in part on Ca2+, calmodulin-dependent protein kinase II (CaMKII) activity. This potentiation of coupling did not require exogenous expression of glutamate receptors, but could be accomplished by endogenously expressed glutamate receptors with pharmacological characteristics reminiscent of NMDA and kainate receptors. Analysis of RNA Sequencing data from HeLa cells confirmed expression of NMDA receptor subunits NR1, NR2C, and NR3B. In summary, Cx36-GCaMP is an effective tool to measure changes in the Ca2+ microenvironment around Cx36 gap junctions. Furthermore, HeLa cells can serve as a model system to study glutamate receptor-driven potentiation of electrical synapses.

Gap Junction Coding Innexin in Lymnaea stagnalis: Sequence Analysis and Characterization in Tissues and the Central Nervous System.

Connections between neurons called synapses are the key components underlying all nervous system functions of animals and humans. However, important genetic information on the formation and plasticity of one type, the electrical (gap junction-mediated) synapse, is understudied in many invertebrates. In the present study, we set forth to identify and characterize the gap junction-encoding gene innexin in the central nervous system (CNS) of the mollusk pond snail Lymnaea stagnalis. With PCR, 3′ and 5′ RACE, and BLAST searches, we identified eight innexin genes in the L. stagnalis genome, named Lst Inx1–Lst Inx8. Phylogenetic analysis revealed that the L. stagnalis innexin genes originated from a single copy in the common ancestor of molluskan species by multiple gene duplication events and have been maintained in L. stagnalis since they were generated. The paralogous innexin genes demonstrate distinct expression patterns among tissues. In addition, one paralog, Lst Inx1, exhibits heterogeneity in cells and ganglia, suggesting the occurrence of functional diversification after gene duplication. These results introduce possibilities to study an intriguing potential relationship between innexin paralog expression and cell-specific functional outputs such as heterogenic ability to form channels and exhibit synapse plasticity. The L. stagnalis CNS contains large neurons and functionally defined networks for behaviors; with the introduction of L. stagnalis in the gap junction gene field, we are providing novel opportunities to combine genetic research with direct investigations of functional outcomes at the cellular, synaptic, and behavioral levels.

Toward the Next Generation of Retinal Neuroprosthesis: Visual Computation with Spikes

A neuroprosthesis is a type of precision medical device that is intended to manipulate the neuronal signals of the brain in a closed-loop fashion, while simultaneously receiving stimuli from the environment and controlling some part of a human brain or body. Incoming visual information can be processed by the brain in millisecond intervals. The retina computes visual scenes and sends its output to the cortex in the form of neuronal spikes for further computation. Thus, the neuronal signal of interest for a retinal neuroprosthesis is the neuronal spike. Closed-loop computation in a neuroprosthesis includes two stages: encoding a stimulus as a neuronal signal, and decoding it back into a stimulus. In this paper, we review some of the recent progress that has been achieved in visual computation models that use spikes to analyze natural scenes that include static images and dynamic videos. We hypothesize that in order to obtain a better understanding of the computational principles in the retina, a hypercircuit view of the retina is necessary, in which the different functional network motifs that have been revealed in the cortex neuronal network are taken into consideration when interacting with the retina. The different building blocks of the retina, which include a diversity of cell types and synaptic connections—both chemical synapses and electrical synapses (gap junctions)—make the retina an ideal neuronal network for adapting the computational techniques that have been developed in artificial intelligence to model the encoding and decoding of visual scenes. An overall systems approach to visual computation with neuronal spikes is necessary in order to advance the next generation of retinal neuroprosthesis as an artificial visual system.

Explosive, continuous and frustrated synchronization transition in spiking Hodgkin–Huxley neural networks: The role of topology and synaptic interaction

Synchronization is an important collective phenomenon in interacting oscillatory agents. Many functional features of the brain are related to synchronization of neurons. The type of synchronization transition that may occur (explosive vs. continuous) has been the focus of intense attention in recent years, mostly in the context of phase oscillator models for which collective behavior is independent of the mean-value of natural frequency. However, synchronization properties of biologically-motivated neural models depend on the firing frequencies. In this study we report a systematic study of gamma-band synchronization in spiking Hodgkin–Huxley neurons which interact via electrical or chemical synapses. We use various network models in order to define the connectivity matrix. We find that the underlying mechanisms and types of synchronization transitions in gamma-band differs from beta-band. In gamma-band, network regularity suppresses transition while randomness promotes a continuous transition. Heterogeneity in the underlying topology does not lead to any change in the order of transition, however, correlation between number of synapses and frequency of a neuron will lead to explosive synchronization in heterogeneous networks with electrical synapses. Furthermore, small-world networks modeling a fine balance between clustering and randomness (as in the cortex), lead to explosive synchronization with electrical synapses, but a smooth transition in the case of chemical synapses. We also find that hierarchical modular networks, such as the connectome, lead to frustrated transitions. We explain our results based on various properties of the network, paying particular attention to the competition between clustering and long-range synapses.

Coexistence of firing patterns and its control in two neurons coupled through an asymmetric electrical synapse.

In this paper, the effects of asymmetry in an electrical synaptic connection between two neuronal oscillators with a small discrepancy are studied in a 2D Hindmarsh-Rose model. We have found that the introduced model possesses a unique unstable equilibrium point. We equally demonstrate that the asymmetric electrical couplings as well as external stimulus induce the coexistence of bifurcations and multiple firing patterns in the coupled neural oscillators. The coexistence of at least two firing patterns including chaotic and periodic ones for some discrete values of coupling strengths and external stimulus is demonstrated using time series, phase portraits, bifurcation diagrams, maximum Lyapunov exponent graphs, and basins of attraction. The PSpice results with an analog electronic circuit are in good agreement with the results of theoretical analyses. Of most/particular interest, multistability observed in the coupled neuronal model is further controlled based on the linear augmentation scheme. Numerical results show the effectiveness of the control strategy through annihilation of the periodic coexisting firing pattern. For higher values of the coupling strength, only a chaotic firing pattern survives. To the best of the authors' knowledge, the results of this work represent the first report on the phenomenon of coexistence of multiple firing patterns and its control ever present in a 2D Hindmarsh-Rose model connected to another one through an asymmetric electrical coupling and, thus, deserves dissemination.

Autonomic learning via saturation gain method, and synchronization between neurons

Synchronization provides an effective way for stable signal exchange and balance in membrane potentials of neurons. Both electric synapse and chemical synapse play important role in processing signals by emitting signal and receiving signals, and the encoded signals are estimated by a variety of synaptic currents. For two or more neurons, the synaptic current can pass along the coupling channels with feasible self-adaption and then synaptic plasticity is formed. The occurrence of synaptic currents generates complex biophysical effect because continuous propagation and pumping of calcium, sodium and potassium can induce time-varying physical field intra- and extracellular of cell. Indeed, the field effect becomes more distinct when more neurons are involved in a functional region of the nervous system. To decrease the energy consumption and obtain fast signal exchange, autonomic learning is often activated to select the most appropriate coupling gain in the synapses connected to neurons. That is, synapse can increase the synaptic intensity carefully before reaching synchronization. In this paper, the two-variable Fitzhugh-Nagumo neuron driven by voltage source is used to investigate the synchronization stability when hybrid synapse is applied between two neurons. By using the saturation gain method, the synapse intensity is increased with appropriate step until synchronization is reached, and then the coupling intensity is fixed to find the threshold for stabilizing complete synchronization. It gives new clues to understand the synaptic plasticity from physical viewpoint.

Reliability of an interneuron response depends on an integrated sensory state.

The central nervous system transforms sensory information into representations that are salient to the animal. Here we define the logic of this transformation in a Caenorhabditis elegans integrating interneuron. AIA interneurons receive input from multiple chemosensory neurons that detect attractive odors. We show that reliable AIA responses require the coincidence of two sensory inputs: activation of AWA olfactory neurons that are activated by attractive odors, and inhibition of one or more chemosensory neurons that are inhibited by attractive odors. AWA activates AIA through an electrical synapse, while the disinhibitory pathway acts through glutamatergic chemical synapses. AIA interneurons have bistable electrophysiological properties consistent with their calcium dynamics, suggesting that AIA activation is a stereotyped response to an integrated stimulus. Our results indicate that AIA interneurons combine sensory information using AND-gate logic, requiring coordinated activity from multiple chemosensory neurons. We propose that AIA encodes positive valence based on an integrated sensory state.

INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans.

In order to respond to changing environments and fluctuations in internal states, animals adjust their behavior through diverse neuromodulatory mechanisms. In this study we show that electrical synapses between the ASH primary quinine-detecting sensory neurons and the neighboring ASK neurons are required for modulating the aversive response to the bitter tastant quinine in C. elegans. Mutant worms that lack the electrical synapse proteins INX-18 and INX-19 become hypersensitive to dilute quinine. Cell-specific rescue experiments indicate that inx-18 operates in ASK while inx-19 is required in both ASK and ASH for proper quinine sensitivity. Imaging analyses find that INX-19 in ASK and ASH localizes to the same regions in the nerve ring, suggesting that both sides of ASK-ASH electrical synapses contain INX-19. While inx-18 and inx-19 mutant animals have a similar behavioral phenotype, several lines of evidence suggest the proteins encoded by these genes play different roles in modulating the aversive quinine response. First, INX-18 and INX-19 localize to different regions of the nerve ring, indicating that they are not present in the same synapses. Second, removing inx-18 disrupts the distribution of INX-19, while removing inx-19 does not alter INX-18 localization. Finally, by using a fluorescent cGMP reporter, we find that INX-18 and INX-19 have distinct roles in establishing cGMP levels in ASK and ASH. Together, these results demonstrate that electrical synapses containing INX-18 and INX-19 facilitate modulation of ASH nociceptive signaling. Our findings support the idea that a network of electrical synapses mediates cGMP exchange between neurons, enabling modulation of sensory responses and behavior.

Gap junctions coordinate the propagation of glycogenolysis induced by norepinephrine in the pineal gland.

Chemical and electrical synapses are the two major communication systems that permit cell-to-cell communication within the nervous system. Although most studies are focused on chemical synapses (glutamate, γ-aminobutyric acid, and other neurotransmitters), clearly both types of synapses interact and cooperate to allow the coordination of several cell functions within the nervous system. The pineal gland has limited independent axonal innervation and not every cell has access to nerve terminals. Thus, additional communication systems, such as gap junctions, have been postulated to coordinate metabolism and signaling. Using acutely isolated glands and dissociated cells, we found that gap junctions spread glycogenolytic signals from cells containing adrenoreceptors to the entire gland lacking these receptors. Our data using glycogen and lactate quantification, electrical stimulation, and high-performance liquid chromatography with electrochemical detection, demonstrate that gap junctional communication between cells of the rat pineal gland allows cell-to-cell propagation of norepinephrine-induced signal that promotes glycogenolysis throughout the entire gland. Thus, the interplay of both synapses is essential for coordinating glycogen metabolism and lactate production in the pineal gland.

Energy estimation and coupling synchronization between biophysical neurons

Static charges can induce spatial electric field while moving charges can induce magnetic field. As a result, continuous pumping and exchange of intercellular and extracellular Calcium, potassium and sodium of cells will generate time-varying magnetic field in the media. Therefore, the physical effect of electromagnetic induction in neural activities should be included in building biological neurons. On the other hand, the occurrence of action potential and propagation of ions require energy consumption and supply, so the estimation of physical energy becomes important. Based on our memristive biophysical neuron model, the Hamilton energy function is obtained by using the Helmholtz’s theorem, and this energy is contributed by the electric field and magnetic field described by magnetic flux. It is found that this improved neuron model can present the main dynamical properties in neural activities, and it characterizes the lower threshold behavior and subthreshold oscillation during refractory period. The external forcing current on an isolate is adjusted to calculate the firing patterns, energy function and mode transition, which shows the dependence of energy on electrical activities. Finally, magnetic coupling is triggered to modulate the phase synchronization between two identical neurons connected by electric synapse, respectively.

Chemical synaptic multiplexing enhances rhythmicity in neuronal networks

Real-world networks are rarely isolated; rather, they constitute a large number of elements interacting through complex topologies and oscillation is essential for their proper functioning. But degradation may come up naturally in such large systems that can severely affect the dynamical activity of the entire network. This mandates us to prescribe some remedies to overcome such deterioration. In this work, we demonstrate this scenario using a neuronal model organized in a framework of multiplex structure composed of a mixture of active and inactive neurons, while interacting via both electrical gap junction and chemical synapse. Multiplex architecture being very much prominent in cortical networks, we explore the simultaneous effect of the electrical and chemical synapses in the persistence of global rhythmicity of a multiplex neuronal network. Our results suggest that although electrical synapse reduces the dynamical performance of the network, chemical synapse through interlayer connection is highly efficient in reviving the rhythmicity of the network. Moreover, we investigate the effect of demultiplexing on the resilience of the network and show that chemical synaptic coupling can revive global rhythmicity under progressive demultiplexing as well. We also demonstrate this effectiveness of the chemical synapses for the case of reverse transition from global rest state to dynamism.

Manipulation of the electrical behaviors of Cu/MXene/SiO2/W memristor

Electronic synapses with both long-term and short-term plasticity are considered as significant components for constructing brain-inspired computing systems. Research progress on electrical synapses have proved that memristors possess huge similarities with biological synapses. Nevertheless, an effective mean of manipulating the biological properties of memristors is still unclear. In this letter, we propose a memristor and reveal that the compliance current of electroforming plays an active role in tuning short-term and long-term plasticity of the memristors. The results may provide a useful guideline for manipulating memristor as electronic synapses in the hardware implementation of artificial neural networks.

Localization of Retinal Ca2+/Calmodulin-Dependent Kinase II-β (CaMKII-β) at Bipolar Cell Gap Junctions and Cross-Reactivity of a Monoclonal Anti-CaMKII-β Antibody With Connexin36.

Neuronal gap junctions formed by connexin36 (Cx36) and chemical synapses share striking similarities in terms of plasticity. Ca2+/calmodulin-dependent protein kinase II (CaMKII), an enzyme known to induce memory formation at chemical synapses, has recently been described to potentiate electrical coupling in the retina and several other brain areas via phosphorylation of Cx36. The contribution of individual CaMKII isoforms to this process, however, remains unknown. We recently identified CaMKII-β at electrical synapses in the mouse retina. Now, we set out to identify cell types containing Cx36 gap junctions that also express CaMKII-β. To ensure precise description, we first tested the specificity of two commercially available antibodies on CaMKII-β-deficient retinas. We found that a polyclonal antibody was highly specific for CaMKII-β. However, a monoclonal antibody (CB-β-1) recognized CaMKII-β but also cross-reacted with the C-terminal tail of Cx36, making localization analyses with this antibody inaccurate. Using the polyclonal antibody, we identified strong CaMKII-β expression in bipolar cell terminals that were secretagogin- and HCN1-positive and thus represent terminals of type 5 bipolar cells. In these terminals, a small fraction of CaMKII-β also colocalized with Cx36. A similar pattern was observed in putative type 6 bipolar cells although there, CaMKII expression seemed less pronounced. Next, we tested whether CaMKII-β influenced the Cx36 expression in bipolar cell terminals by quantifying the number and size of Cx36-immunoreactive puncta in CaMKII-β-deficient retinas. However, we found no significant differences between the genotypes, indicating that CaMKII-β is not necessary for the formation and maintenance of Cx36-containing gap junctions in the retina. In addition, in wild-type retinas, we observed frequent association of Cx36 and CaMKII-β with synaptic ribbons, i.e., chemical synapses, in bipolar cell terminals. This arrangement resembled the composition of mixed synapses found for example in Mauthner cells, in which electrical coupling is regulated by glutamatergic activity. Taken together, our data imply that CaMKII-β may fulfill several functions in bipolar cell terminals, regulating both Cx36-containing gap junctions and ribbon synapses and potentially also mediating cross-talk between these two types of bipolar cell outputs.