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• Connexin36 is highly expressed in sympathetic preganglionic neurons (SPNs). • Connnexin36 is detected along the entire length of the spinal thoracic intermediolateral cell column. • The IML contains glutamatergic and GABAergic terminals that are eGFP+ in Cx36BAC::eGFP mice. • SPNs are innervated by eGFP+ terminals in Cx36BAC::eGFP mice. Spinal sympathetic preganglionic neurons (SPNs) are among the many neuronal populations in the mammalian central nervous system (CNS) where there is evidence for electrical coupling between cell pairs linked by gap junctions composed of connexin36 (Cx36). Understanding the organization of this coupling in relation to autonomic functions of spinal sympathetic systems requires knowledge of how these junctions are deployed among SPNs. Here, we document the distribution of immunofluorescence detection of Cx36 among SPNs identified by immunolabelling of their various markers, including choline acetyltransferase, nitric oxide and peripherin in adult and developing mouse and rat. In adult animals, labelling of Cx36 was exclusively punctate and dense concentrations of Cx36-puncta were distributed along the entire length of the spinal thoracic intermediolateral cell column (IML). These puncta were also seen in association with SPN dendritic processes in the lateral funiculus, the intercalated and central autonomic areas and those within and extending medially from the IML. All labelling for Cx36 was absent in spinal cords of Cx36 knockout mice. High densities of Cx36-puncta were already evident among clusters of SPNs in the IML of mouse and rat at postnatal days 10–12. In Cx36BAC::eGFP mice, eGFP reporter was absent in SPNs, thus representing false negative detection, but was localized to some glutamatergic and GABAergic synaptic terminals. Some eGFP+ terminals were found contacting SPN dendrites. These results indicate widespread Cx36 expression in SPNs, further supporting evidence of electrical coupling between these cells, and suggest that SPNs are innervated by neurons that themselves may be electrically coupled. [ABSTRACT FROM AUTHOR]

The inferior olivary (IO) nucleus makes up the signal gateway for several organs to the cerebellar cortex. Located within the sensory–motor-cerebellum pathway, the IO axons, i.e., climbing fibres (CFs), massively synapse onto the cerebellar Purkinje cells (PCs) regulating motor learning whilst the olivary nucleus receives negative feedback through the GABAergic nucleo-olivary​ (NO) pathway. The NO pathway regulates the electrical coupling (EC) amongst the olivary cells thus facilitating synchrony and timing. However, the involvement of this EC regulation on cerebellar adaptive behaviour is still under debate. In our study we have used a spiking cerebellar model to assess the role of the NO pathway in regulating vestibulo-ocular-reflex (VOR) adaptation. The model incorporates spike-based synaptic plasticity at multiple cerebellar sites and an electrically-coupled olivary system. The olivary system plays a central role in regulating the CF spike-firing patterns that drive the PCs, whose axons ultimately shape the cerebellar output. Our results suggest that a systematic GABAergic NO deactivation decreases the spatio-temporal complexity of the IO firing patterns thereby worsening the temporal resolution of the olivary system. Conversely, properly coded IO spatio-temporal firing patterns, thanks to NO modulation, finely shape the balance between long-term depression and potentiation, which optimises VOR adaptation. Significantly, the NO connectivity pattern constrained to the same micro-zone helps maintain the spatio-temporal complexity of the IO firing patterns through time. Moreover, the temporal alignment between the latencies found in the NO fibres and the sensory–motor pathway delay appears to be crucial for facilitating the VOR. When we consider all the above points we believe that these results predict that the NO pathway is instrumental in modulating the olivary coupling and relevant to VOR adaptation. [ABSTRACT FROM AUTHOR]

• Subpopulations of cholinergic V0c neurons in the spinal cord of Cx36BAC-eGFP mice express eGFP. • The eGFP+ V0c neurons were identified by their expression of the transcription factor Pitx2. • The eGFP+ subset of V0c neurons receive dense serotonergic innervation. • Evidence suggests that a subset of V0c neurons is coupled by Cx36-containing gap junctions. • C-terminals arising from eGFP+ V0c neurons preferentially innervate fast vs. slow motoneurons. Large cholinergic neurons (V0c neurons; aka, partition cells) in the spinal cord project profusely to motoneurons on which they form C-terminal contacts distinguished by their specialized postsynaptic subsurface cisterns (SSCs). The V0c neurons are known to be rhythmically active during locomotion and release of acetylcholine (ACh) from their terminals is known to modulate the excitability of motoneurons in what appears to be a task-dependent manner. Here, we present evidence that a subpopulation of V0c neurons express the gap junction forming protein connexin36 (Cx36), indicating that they are coupled by electrical synapses. Based on immunofluorescence imaging and the use of Cx36BAC-enhanced green fluorescent protein (eGFP) mice in which C-terminals immunolabelled for their marker vesicular acetylcholine transporter (vAChT) are also labelled for eGFP, we found a heterogeneous distribution of eGFP+ C-terminals on motoneurons at cervical, thoracic and lumber spinal levels. The density of C-terminals on motoneurons varied as did the proportion of those that were eGFP+ vs. eGFP−. We present evidence that fast vs. slow motoneurons have a greater abundance of these terminals and fast motoneurons also have the highest density that were eGFP+. Thus, our results indicate that a subpopulation of V0c neurons projects preferentially to fast motoneurons, suggesting that the capacity for synchronous activity conferred by electrical synapses among networks of coupled V0c neurons enhances their dynamic capabilities for synchronous regulation of motoneuron excitability during high muscle force generation. The eGFP+ vs. eGFP− V0c neurons were more richly innervated by serotonergic terminals, suggesting their greater propensity for regulation by descending serotonergic systems. [ABSTRACT FROM AUTHOR]

The vestibulo-ocular reflex (VOR) stabilizes vision during head motion. Age-related changes of vestibular neuroanatomical properties predict a linear decay of VOR function. Nonetheless, human epidemiological data show a stable VOR function across the life span. In this study, we model cerebellum-dependent VOR adaptation to relate structural and functional changes throughout aging. We consider three neurosynaptic factors that may codetermine VOR adaptation during aging: the electrical coupling of inferior olive neurons, the long-term spike timing-dependent plasticity at parallel fiber – Purkinje cell synapses and mossy fiber – medial vestibular nuclei synapses, and the intrinsic plasticity of Purkinje cell synapses Our cross-sectional aging analyses suggest that long-term plasticity acts as a global homeostatic mechanism that underpins the stable temporal profile of VOR function. The results also suggest that the intrinsic plasticity of Purkinje cell synapses operates as a local homeostatic mechanism that further sustains the VOR at older ages. Importantly, the computational epidemiology approach presented in this study allows discrepancies among human cross-sectional studies to be understood in terms of interindividual variability in older individuals. Finally, our longitudinal aging simulations show that the amount of residual fibers coding for the peak and trough of the VOR cycle constitutes a predictive hallmark of VOR trajectories over a lifetime. [ABSTRACT FROM AUTHOR]

• Molecular layer interneurons (MLIs) participate in spatially structured networks via chemical and electrical synapses. • Clusters of MLIs converge to control the temporal and spatial pattern of Purkinje cell activity in cerebellum. • These MLI circuits mediate a number of behavioral functions, including motor coordination and learning. Molecular layer interneurons (MLIs) play an important role in cerebellar information processing by controlling Purkinje cell (PC) activity via inhibitory synaptic transmission. A local MLI network, constructed from both chemical and electrical synapses, is organized into spatially structured clusters that amplify feedforward and lateral inhibition to shape the temporal and spatial patterns of PC activity. Several recent in vivo studies indicate that such MLI circuits contribute not only to sensorimotor information processing, but also to precise motor coordination and cognitive processes. Here, we review current understanding of the organization of MLI circuits and their roles in the function of the mammalian cerebellum. [ABSTRACT FROM AUTHOR]

Acquired temporal lobe epilepsy (TLE) characterized by spontaneous recurrent seizures (SRS) and hippocampal inhibitory neuron dysfunction is often refractory to current therapies. Gap junctional or electrical coupling between inhibitory neurons has been proposed to facilitate network synchrony and intercellular molecular exchange suggesting a role in both seizures and neurodegeneration. While gap junction blockers can limit acute seizures, whether blocking neuronal gap junctions can modify development of chronic epilepsy has not been examined. This study examined whether mefloquine, a selective blocker of Connexin 36 gap junctions which are well characterized in inhibitory neurons, can limit epileptogenesis and related cellular and behavioral pathology in a model of acquired TLE. A single, systemic dose of mefloquine administered early after pilocarpine-induced status epilepticus (SE) in rat reduced both development of SRS and behavioral co-morbidities. Immunostaining for interneuron subtypes identified that mefloquine treatment likely reduced delayed inhibitory neuronal loss after SE. Uniquely, parvalbumin expressing neurons in the hippocampal dentate gyrus appeared relatively resistant to early cell loss after SE. Functionally, whole cell patch clamp recordings revealed that mefloquine treatment preserved inhibitory synaptic drive to projection neurons one week and one month after SE. These results demonstrate that mefloquine, a drug already approved for malaria prophylaxis, is potentially antiepileptogenic and can protect against progressive interneuron loss and behavioral co-morbidities of epilepsy. • Single dose mefloquine treatment after an acute seizure reduces development of spontaneous recurrent seizures. • Mefloquine treatment after seizure protects against delayed interneuron loss with cell-type and regional specificity. • Functionally, mefloquine treatment preserved inhibitory synaptic drive to projection neurons after SE. [ABSTRACT FROM AUTHOR]

Intimate structural and functional relationships between gap junctions and adherens junctions have been demonstrated in peripheral tissues, but have not been thoroughly examined in the central nervous system, where adherens junctions are often found in close proximity to neuronal gap junctions. Here, we used immunofluorescence approaches to document the localization of various protein components of adherens junctions in relation to those that we have previously reported to occur at electrical synapses formed by neuronal gap junctions composed of connexin36 (Cx36). The adherens junction constituents N-cadherin and nectin-1 were frequently found to localize near or overlap with Cx36-containing gap junctions in several brain regions examined. This was also true of the adherens junction-associated proteins α-catenin and β-catenin, as well as the proteins zonula occludens-1 and AF6 (aka, afadin) that were reported constituents of both adherens junctions and gap junctions. The deployment of the protein constituents of these junctions was especially striking at somatic contacts between primary afferent neurons in the mesencephalic trigeminal nucleus (MesV), where the structural components of adherens junctions appeared to be maintained in connexin36 null mice. These results support emerging views concerning the multi-molecular composition of electrical synapses and raise possibilities for various structural and functional protein–protein interactions at what now can be considered the adherens junction–neuronal gap junction complex. Further, the results point to intracellular signaling pathways that could potentially contribute to the assembly, maintenance and turnover of this complex, as well as to the dynamic nature of neuronal communication at electrical synapses. [ABSTRACT FROM AUTHOR]

Circadian (24-h) clocks are cell-autonomous biological oscillators that orchestrate many aspects of our physiology on a daily basis. Numerous circadian rhythms in mammalian and non-mammalian retinas have been observed and the presence of an endogenous circadian clock has been demonstrated. However, how the clock and associated rhythms assemble into pathways that support and control retina function remains largely unknown. Our goal here is to review the current status of our knowledge and evaluate recent advances. We describe many previously-observed retinal rhythms, including circadian rhythms of morphology, biochemistry, physiology, and gene expression. We evaluate evidence concerning the location and molecular machinery of the retinal circadian clock, as well as consider findings that suggest the presence of multiple clocks. Our primary focus though is to describe in depth circadian rhythms in the light responses of retinal neurons with an emphasis on clock control of rod and cone pathways. We examine evidence that specific biochemical mechanisms produce these daily light response changes. We also discuss evidence for the presence of multiple circadian retinal pathways involving rhythms in neurotransmitter activity, transmitter receptors, metabolism, and pH. We focus on distinct actions of two dopamine receptor systems in the outer retina, a dopamine D 4 receptor system that mediates circadian control of rod/cone gap junction coupling and a dopamine D 1 receptor system that mediates non-circadian, light/dark adaptive regulation of gap junction coupling between horizontal cells. Finally, we evaluate the role of circadian rhythmicity in retinal degeneration and suggest future directions for the field of retinal circadian biology. [ABSTRACT FROM AUTHOR]

• SIF cells in cardiac parasympathetic ganglia of adult mice and rats express Cx36. • Connexin36 was detected in SIF cells early during development. • Enhanced green fluorescent protein reporter for Cx36 expression was detected in SIF cells. • Immunofluorescent Cx36-puncta appeared at appositions between SIF cells. • SIF cells may express Cx36-containing gap junctions to coordinate hormonal secretion. In mammals, several endocrine cell types are electrically coupled by connexin36 (Cx36)-containing gap junctions, which mediate intercellular communication and allow regulated and synchronized cellular activity through exchange of ions and small metabolites via formation of intercellular channels that link plasma membranes of apposing cells. One cell type thought to be endocrine-like in nature are small intensely fluorescent (SIF) cells that store catecholamines in their dense-core vesicles and reside in autonomic ganglia. Here, using immunofluorescence approaches, we examined whether SIF cells located specifically in cardiac parasympathetic ganglia of adult and neonatal mice and adult rats follow patterns of Cx36 expression seen in other endocrine cells. In these ganglia, SIF cells were identified by their distinct small soma size, autofluorescence at 475 nm, and immunolabelling for their markers tyrosine hydroxylase and vesicular monoamine transporter-1. SIF cells were often found in pairs or clusters among principal cholinergic neurons. Immunofluorescence labelling of Cx36 occurred exclusively as fine puncta that appeared at contacts between SIF cell processes and somata or at somato-somatic appositions of SIF cells. These puncta were absent in cardiac parasympathetic ganglia of Cx36 null mice. Transgenic mice expressing enhanced green fluorescent protein reporter for Cx36 expression displayed labelling for the reporter in SIF cells. The results suggest that Cx36-containing gap junctions electrically couple SIF cells, which is consistent with previous suggestions that these may be classified as endocrine-type cells that secrete catecholamines into the bloodstream in a regulated manner. [ABSTRACT FROM AUTHOR]

Electrical synapses formed by gap junctions composed of connexin36 (Cx36) are widely distributed in the mammalian central nervous system (CNS). Here, we used immunofluorescence methods to document the expression of Cx36 in the cochlear nucleus and in various structures of the auditory pathway of rat and mouse. Labeling of Cx36 visualized exclusively as Cx36-puncta was densely distributed primarily on the somata and initial dendrites of neuronal populations in the ventral cochlear nucleus, and was abundant in superficial layers of the dorsal cochlear nucleus. Other auditory centers displaying Cx36-puncta included the medial nucleus of the trapezoid body (MNTB), regions surrounding the lateral superior olivary nucleus, the dorsal nucleus of the medial lemniscus, the nucleus sagulum, all subnuclei of the inferior colliculus, and the auditory cerebral cortex. In EGFP-Cx36 transgenic mice, EGFP reporter was detected in neurons located in each of auditory centers that harbored Cx36-puncta. In the ventral cochlear nuclei and the MNTB, many neuronal somata were heavily innervated by nerve terminals containing vesicular glutamate transporter-1 (vglut1) and Cx36 was frequently localized at these terminals. Cochlear ablation caused a near total depletion of vglut1-positive terminals in the ventral cochlear nuclei, with a commensurate loss of labeling for Cx36 around most neuronal somata, but preserved Cx36-puncta at somatic neuronal appositions. The results suggest that electrical synapses formed by Cx36-containing gap junctions occur in most of the widely distributed centers of the auditory system. Further, it appears that morphologically mixed chemical/electrical synapses formed by nerve terminals are abundant in the ventral cochlear nucleus, including those at endbulbs of Held formed by cochlear primary afferent fibers, and those at calyx of Held synapses on MNTB neurons. [ABSTRACT FROM AUTHOR]

We investigate the capability of electrical synapses to transmit the noise-sustained network activity from one network to another. The particular setup we consider is two identical rings with excitable FitzHugh–Nagumo cell dynamics and nearest-neighbor antiphase intra-ring coupling, electrically coupled between corresponding nodes. The whole system is submitted to independent local additive Gaussian white noises with common intensity η , but only one ring is externally forced by a global adiabatic subthreshold harmonic signal. We then seek conditions for a particular noise level to promote synchronized stable firing patterns. By running numerical integrations with increasing η , we observe the excitation activity to become spatiotemporally self-organized, until η is so strong that spoils sync between networks for a given value of the electric coupling strength. By means of a four-cell model and calculating the stationary probability distribution, we obtain a (signal-dependent) non-equilibrium potential landscape which explains qualitatively the observed regimes, and whose barrier heights give a good estimate of the optimal noise intensity for the sync between networks. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cx36 is abundant in the vestibular nuclei (VN) of rat and mouse. [•] Cx36 is localized to sites of contact between axon terminals and VN neurons. [•] Axon terminals displaying Cx36 in VN are of primary afferent origin. [•] Mixed synapses in the VN had a relatively late appearance developmentally. [Copyright &y& Elsevier]

Abstract: We study the firing rate properties of a cellular automaton model for a neuronal network with chemical synapses. We propose a simple mechanism in which the nonlocal connections are included, through electrical and chemical synapses. In the latter case, we introduce a time delay which produces self-sustained activity. Nonlocal connections, or shortcuts, are randomly introduced according to a specified connection probability. There is a range of connection probabilities for which neuron firing occurs, as well as a critical probability for which the firing ceases in the absence of time delay. The critical probability for nonlocal shortcuts depends on the network size according to a power-law. We also compute the firing rate amplification factor by varying both the connection probability and the time delay for different network sizes. [Copyright &y& Elsevier]

Abstract: Gap junctions play an important role in brain physiology. They synchronize neuronal activity and connect glial cells participating in the regulation of brain metabolism and homeostasis. Gap junction blockers (GJBs) include various chemicals that impair gap junction communication, disrupt oscillatory neuronal activity over a wide range of frequencies, and decrease epileptic discharges. The behavioural and clinical effects of GJBs suggest that gap junctions can be involved in the regulation of locomotor activity, arousal, memory, and breathing. Severe neuropsychiatric side effects suggest the involvement of gap junctions in mechanisms of consciousness. Unfortunately, the available GJBs are not selective and can bind to targets other than gap junctions. Other problems in behavioural studies include the possible adverse effects of GJBs, for example, retinal toxicity and hearing disturbances, changes in blood-brain transport, and the metabolism of other drugs. Therefore, it is necessary to design experiments properly to avoid false, misleading or uninterpretable results. We review the pharmacological properties and electrophysiological, behavioural and cognitive effects of the available gap junction blockers, such as carbenoxolone, glycyrrhetinic acid, quinine, quinidine, mefloquine, heptanol, octanol, anandamide, fenamates, 2-APB, several anaesthetics, retinoic acid, oleamide, spermine, aminosulfonates, and sodium propionate. It is concluded that despite a number of different problems, the currently used gap junction blockers could be useful tools in pharmacology and neuroscience. [Copyright &y& Elsevier]

Abstract: The Mauthner (M-) cells are pair of large reticulospinal neurons that mediate tail-flip escape responses in fish. Exploring the co-localization of scaffold and gap junction proteins at mixed (electrical and chemical) synapses, we found that the use of a particular antibody against the scaffold protein Zonula Occludens-2 (ZO-2) resulted in labeling of these cells. We show here that this staining is restricted to the Mauthner cell and evenly distributed along its dendrites and axon, also prominent in small dendritic and axonal processes. Because the observed labeling is non-specific, we suggest that the antibody might recognize a soluble protein that is primarily expressed in the Mauthner cells. While the identity of this protein is presently unknown, the use of this antibody should facilitate the identification of the Mauthner cell and its fine processes during anatomical and immunohistochemical studies, which otherwise require intracellular injection of tracer molecules during electrophysiological recordings. [Copyright &y& Elsevier]

Abstract: Most gap junctions between neurons in mammalian retina contain abundant connexin36, often in association with the scaffolding protein zonula occludens-1. We now investigate co-association of connexin36, zonula occludens-1, zonula occludens-2 and Y-box transcription factor 3 (zonula occludens-1-associated nucleic acid-binding protein) in mouse and rat retina. By immunoblotting, zonula occludens-1-associated nucleic acid-binding protein and zonula occludens-2 were both detected in retina, and zonula occludens-2 in retina was found to co-immunoprecipitate with connexin36. By immunofluorescence, the four proteins appeared as puncta distributed in the plexiform layers. In the inner plexiform layer, most connexin36-puncta were co-localized with zonula occludens-1, and many were co-localized with zonula occludens-1-associated nucleic acid-binding protein. Moreover, zonula occludens-1-associated nucleic acid-binding protein was often co-localized with zonula occludens-1. Nearly all zonula occludens-2-puncta were positive for connexin36, zonula occludens-1 and zonula occludens-1-associated nucleic acid-binding protein. In the outer plexiform layer, connexin36 was also often co-localized with zonula occludens-1-associated nucleic acid-binding protein. In connexin36 knockout mice, labeling of zonula occludens-1 was slightly reduced in the inner plexiform layer, zonula occludens-1-associated nucleic acid-binding protein was decreased in the outer plexiform layer, and both zonula occludens-1-associated nucleic acid-binding protein and zonula occludens-2 were markedly decreased in the inner sublamina of the inner plexiform layer, whereas zonula occludens-1, zonula occludens-2 and zonula occludens-1-associated nucleic acid-binding protein puncta persisted and remained co-localized in the outer sublamina of the inner plexiform layer. By freeze-fracture replica immunogold labeling, connexin36 was found to be co-localized with zonula occludens-2 within individual neuronal gap junctions. In addition, zonula occludens-1-associated nucleic acid-binding protein was abundant in a portion of ultrastructurally-defined gap junctions throughout the inner plexiform layer, and some of these junctions contained both connexin36 and zonula occludens-1-associated nucleic acid-binding protein. These distinct patterns of connexin36 association with zonula occludens-1, zonula occludens-2 and zonula occludens-1-associated nucleic acid-binding protein in different sublaminae of retina, and differential responses of these proteins to connexin36 gene deletion suggest differential regulatory and scaffolding roles of these gap junction accessory proteins. Further, the persistence of a subpopulation of zonula occludens-1/zonula occludens-2/zonula occludens-1-associated nucleic acid-binding protein co-localized puncta in the outer part of the inner plexiform layer of connexin36 knockout mice suggests close association of these proteins with other structures in retina, possibly including gap junctions composed of an as-yet-unidentified connexin. [Copyright &y& Elsevier]

Recent evidence indicates the presence of gap junctions in the olfactory epithelium (OE). This raises the possibility that olfactory receptor neurons (ORNs) might be coupled by electrical synapses. If this scenario is true, propagating self-sustained activity waves might exist in the OE. To investigate this hypothesis a computer model of the olfactory epithelium was constructed consisting of a grid of ORNs connected by electrical synapses receiving simulated odor input. The results challenge the view that odor identity coding in the OE is purely spatial, suggesting that a more complex odor coding scheme involving time might be used by the OE. [Copyright &y& Elsevier]

In recent years, several key studies have shed new light on the roles of electrical signaling via gap junctions between neurons in the adult brain. In particular, it is now clear that electrical signaling is important, if not essential, for the generation of a wide variety of different network interactions which may underlie rhythmic activity, of cognitive relevance, seen in EEG recordings. Two types of such rhythmic activity observed in the hippocampus both in vivo and in vitro are gamma frequency (30–80 Hz) oscillations and ultrafast (>80 Hz) “ripple” oscillations. Several lines of work, discussed here, show that gap junction-mediated signaling plays a central role in the generation of both these types of network activity. Recent work also now suggests that a number of different, anatomically discrete, gap junction-mediated networks may exist which could both function and be modulated independently. [Copyright &y& Elsevier]

Gap junctions are widely expressed in the various cell types of the central nervous system. These specialized membrane intercellular junctions provide the morphological support for direct electrical and biochemical communication between adjacent cells. This intercellular coupling is controlled by neurotransmitters and other endogenous compounds produced and released in basal as well as in pathological situations. Changes in the expression and the function of connexins are associated with number of brain pathologies and lesions suggesting that they could contribute to the expansion of brain damages. The purpose of this review is to summarize data presently available concerning gap junctions and the expression and function of connexins in different cell types of the central nervous system and to present their physiopathological relevance in three major brain dysfunctions: inflammation, epilepsy and ischemia. [Copyright &y& Elsevier]

Our understanding of nervous system function is limited by our ability to identify and manipulate neuronal subtypes within intact circuits. We show that the Gbx2 CreERT2-IRES-EGFP mouse line labels two amacrine cell (AC) subtypes in the mouse retina that have distinct morphological, physiological, and molecular properties. Using a combination of RNA-seq, genetic labeling, and patch clamp recordings, we show that one subtype is GABAergic that receives excitatory input from On bipolar cells. The other population is a non-GABAergic, non-glycinergic (nGnG) AC subtype that lacks the expression of standard neurotransmitter markers. Gbx2+ nGnG ACs have smaller, asymmetric dendritic arbors that receive excitatory input from both On and Off bipolar cells. Gbx2+ nGnG ACs also exhibit spatially restricted tracer coupling to bipolar cells (BCs) through gap junctions. This study identifies a genetic tool for investigating the two distinct AC subtypes, and it provides a model for studying synaptic communication and visual circuit function. • Gbx2 identifies two amacrine cell interneurons in the mouse retina • The Gbx2+ subtypes are molecularly, morphologically, and physiologically distinct • One Gbx2+ subtype lacks classical neurotransmitters but has electrical synapses Investigations into neural circuit development and function are limited by the lack of genetic tools to label and perturb individual neuronal subtypes. Using the Gbx2 CreERT2 mouse line, Kerstein et al. identify two amacrine cell subtypes in the mouse retina and explore their distinct molecular, morphological, and physiological characteristics. [ABSTRACT FROM AUTHOR]