Trophoblast glycoprotein is required for efficient synaptic vesicle exocytosis from retinal rod bipolar cells.

Introduction: Rod bipolar cells (RBCs) faithfully transmit light-driven signals from rod photoreceptors in the outer retina to third order neurons in the inner retina. Recently, significant work has focused on the role of leucine-rich repeat (LRR) proteins in synaptic development and signal transduction at RBC synapses. We previously identified trophoblast glycoprotein (TPBG) as a novel transmembrane LRR protein localized to the dendrites and axon terminals of RBCs.

Functional maturation of the rod bipolar to AII-amacrine cell ribbon synapse in the mouse retina.

Retinal ribbon synapses undergo functional changes after eye opening that remain uncharacterized. Using light-flash stimulation and paired patch-clamp recordings, we examined the maturation of the ribbon synapse between rod bipolar cells (RBCs) and AII-amacrine cells (AII-ACs) after eye opening (postnatal day 14) in the mouse retina at near physiological temperatures. We find that light-evoked excitatory postsynaptic currents (EPSCs) in AII-ACs exhibit a slow sustained component that increases in magnitude with advancing age, whereas a fast transient component remains unchanged.

Cell type specializations of the vocal-motor cortex in songbirds.

Identifying molecular specializations in cortical circuitry supporting complex behaviors, like learned vocalizations, requires understanding of the neuroanatomical context from which these circuits arise. In songbirds, the robust arcopallial nucleus (RA) provides descending cortical projections for fine vocal-motor control. Using single-nuclei transcriptomics and spatial gene expression mapping in zebra finches, we have defined cell types and molecular specializations that distinguish RA from adjacent regions involved in non-vocal motor and sensory processing.

Motor cortex analogue neurons in songbirds utilize Kv3 channels to generate ultranarrow spikes.

Complex motor skills in vertebrates require specialized upper motor neurons with precise action potential (AP) firing. To examine how diverse populations of upper motor neurons subserve distinct functions and the specific repertoire of ion channels involved, we conducted a thorough study of the excitability of upper motor neurons controlling somatic motor function in the zebra finch. We found that robustus arcopallialis projection neurons (RAPNs), key command neurons for song production, exhibit ultranarrow spikes and higher firing rates compared to neurons controlling non-vocal somatic motor functions (dorsal intermediate arcopallium [AId] neurons).

A melanopsin ganglion cell subtype forms a dorsal retinal mosaic projecting to the supraoptic nucleus.

Visual input to the hypothalamus from intrinsically photosensitive retinal ganglion cells (ipRGCs) influences several functions including circadian entrainment, body temperature, and sleep. ipRGCs also project to nuclei such as the supraoptic nucleus (SON), which is involved in systemic fluid homeostasis, maternal behavior, social behaviors, and appetite. However, little is known about the SON-projecting ipRGCs or their relationship to well-characterized ipRGC subtypes.

Resurgent Na currents promote ultrafast spiking in projection neurons that drive fine motor control.

The underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood. Here we report that projection neurons in the adult zebra finch song nucleus RA display robust high-frequency firing, ultra-narrow spike waveforms, superfast Na current inactivation kinetics, and large resurgent Na currents (I). These properties of songbird pallial motor neurons closely resemble those of specialized large pyramidal neurons in mammalian primary motor cortex.

Glycine Release Is Potentiated by cAMP via EPAC2 and Ca Stores in a Retinal Interneuron.

Neuromodulation via the intracellular second messenger cAMP is ubiquitous at presynaptic nerve terminals. This modulation of synaptic transmission allows exocytosis to adapt to stimulus levels and reliably encode information. The AII amacrine cell (AII-AC) is a central hub for signal processing in the mammalian retina.

Molecular mechanism of prestin electromotive signal amplification.

Hearing involves two fundamental processes: mechano-electrical transduction and signal amplification. Despite decades of studies, the molecular bases for both remain elusive. Here, we show how prestin, the electromotive molecule of outer hair cells (OHCs) that senses both voltage and membrane tension, mediates signal amplification by coupling conformational changes to alterations in membrane surface area.

Encoding sound in the cochlea: from receptor potential to afferent discharge.

Ribbon-class synapses in the ear achieve analog to digital transformation of a continuously graded membrane potential to all-or-none spikes. In mammals, several auditory nerve fibres (ANFs) carry information from each inner hair cell (IHC) to the brain in parallel. Heterogeneity of transmission among synapses contributes to the diversity of ANF sound-response properties.

How to Build a Fast and Highly Sensitive Sound Detector That Remains Robust to Temperature Shifts.

Frogs must have sharp hearing abilities during the warm summer months to successfully find mating partners. This study aims to understand how frog hair cell ribbon-type synapses preserve both sensitivity and temporal precision during temperature changes. Under room (∼24°C) and high (∼32°C) temperature, we performed patch-clamp recordings of hair cells and their afferent fibers in amphibian papillae of either male or female bullfrogs.

Presynaptic Diversity Revealed by Ca-Permeable AMPA Receptors at the Calyx of Held Synapse.

GluA2-lacking Ca-permeable AMPARs (CP-AMPARs) play integral roles in synaptic plasticity and can mediate excitotoxic cellular signaling at glutamatergic synapses. However, the developmental profile of functional CP-AMPARs at the auditory brainstem remains poorly understood. Through a combination of electrophysiological and live-cell Ca imaging from mice of either sex, we show that the synaptic release of glutamate from the calyx of Held nerve terminal activates CP-AMPARs in the principal cells of the medial nucleus of the trapezoid body in the brainstem.

Clustered Ca Channels Are Blocked by Synaptic Vesicle Proton Release at Mammalian Auditory Ribbon Synapses.

A Ca current transient block (ITB) by protons occurs at some ribbon-type synapses after exocytosis, but this has not been observed at mammalian hair cells. Here we show that a robust ITB occurs at post-hearing mouse and gerbil inner hair cell (IHC) synapses, but not in immature IHC synapses, which contain non-compact active zones, where Ca channels are loosely coupled to the release sites. Unlike ITB at other ribbon synapses, ITB in mammalian IHCs displays a surprising multi-peak structure that mirrors the EPSCs seen in paired recordings.

Vision: Microcircuits Rage against the Dimming of the Light.

At sundown when light levels fall, rod photoreceptors take the night shift from the daylight-sensitive cones and a specialized mammalian microcircuit 'wires' the rods into the ancestral cone pathway. A recent study combines serial electron microscopy and simultaneous patch clamp recordings to shed light on this microcircuit in unprecedented detail.

Ca-Permeable AMPARs Mediate Glutamatergic Transmission and Excitotoxic Damage at the Hair Cell Ribbon Synapse.

We report functional and structural evidence for GluA2-lacking Ca-permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By using the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of electrophysiological and Ca imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca influx into afferent terminals.

Distinct Actions of Voltage-Activated Ca Channel Block on Spontaneous Release at Excitatory and Inhibitory Central Synapses.

At chemical synapses, voltage-activated calcium channels (VACCs) mediate Ca influx to trigger action potential-evoked neurotransmitter release. However, the mechanisms by which Ca regulates spontaneous transmission have not been fully determined. We have shown that VACCs are a major trigger of spontaneous release at neocortical inhibitory synapses but not at excitatory synapses, suggesting fundamental differences in spontaneous neurotransmission at GABAergic and glutamatergic synapses.

The Coupling between Ca Channels and the Exocytotic Ca Sensor at Hair Cell Ribbon Synapses Varies Tonotopically along the Mature Cochlea.

The cochlea processes auditory signals over a wide range of frequencies and intensities. However, the transfer characteristics at hair cell ribbon synapses are still poorly understood at different frequency locations along the cochlea. Using recordings from mature gerbils, we report here a surprisingly strong block of exocytosis by the slow Ca buffer EGTA (10 mM) in basal hair cells tuned to high frequencies (∼30 kHz).

Recycling at synapses.

Synaptic vesicles in rodent neurons are recycled using at least two distinct mechanisms.

Fast, Temperature-Sensitive and Clathrin-Independent Endocytosis at Central Synapses.

The fusion of neurotransmitter-filled vesicles during synaptic transmission is balanced by endocytotic membrane retrieval. Despite extensive research, the speed and mechanisms of synaptic vesicle endocytosis have remained controversial. Here, we establish low-noise time-resolved membrane capacitance measurements that allow monitoring changes in surface membrane area elicited by single action potentials and stronger stimuli with high-temporal resolution at physiological temperature in individual bona-fide mature central synapses.

Postsynaptic Plasticity Triggered by Ca²⁺-Permeable AMPA Receptor Activation in Retinal Amacrine Cells.

Amacrine cells are thought to be a major locus for mechanisms of light adaptation and contrast enhancement in the retina. However, the potential for plasticity in their AMPA receptor currents remains largely unknown. Using paired patch-clamp recordings between bipolar cell terminals and amacrine cells, we have simultaneously measured presynaptic membrane capacitance changes and EPSCs.

Synaptic Vesicle Exocytosis at the Dendritic Lobules of an Inhibitory Interneuron in the Mammalian Retina.

Ribbon synapses convey sustained and phasic excitatory drive within retinal microcircuits. However, the properties of retinal inhibitory synapses are less well known. AII-amacrine cells are interneurons in the retina that exhibit large glycinergic synapses at their dendritic lobular appendages.