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A well-established AII amacrine cell model linked to blinding retinal diseases demonstrates rhythmic bursting activity. This behavior potentially impedes the retinal and cortical responses essential for visual restoration. Consequently, understanding the dynamics of AII amacrine cell firing is critical. We expanded the study by incorporating a calcium ion channel into the original model, creating a refined eight-dimensional AII model. This enhancement allowed us to conduct an in-depth exploration of system behavior via bifurcation analysis and an extensive examination of multi-timescale singularities. We identified the parameter ranges that control the firing activities of the model through codimension-one and codimension-two bifurcation analyses of key parameters. Furthermore, our research revealed that introducing a balance equation determines a transition from regular spiking to bursting. Importantly, the orchestration of three-timescale spiking and bursting attractors is enabled by the universal unfolding of the winged cusp singularity. This study provides a comprehensive analysis of firing dynamics in a high-dimensional neuron model. The insights derived significantly advance our understanding the dynamical behaviors of AII amacrine cells and are promising for improving strategies for retinal pathologies. [ABSTRACT FROM AUTHOR]

Congenital nystagmus is a condition where the eyes of patients oscillate, mostly horizontally, with a frequency of between 2 and 10 Hz. Historically, nystagmus is believed to be caused by a maladaptation of the oculomotor system and is thus considered a disease of the brain stem. However, we have recently shown that congenital nystagmus associated with congenital stationary night blindness is caused by synchronously oscillating retinal ganglion cells. In this perspective article, we discuss how some details of nystagmus can be accounted for by the retinal mechanism we propose.

Amacrine cells are a highly diverse group of inhibitory retinal interneurons that sculpt the responses of bipolar cells, ganglion cells, and other amacrine cells. They integrate excitatory inputs from bipolar cells and inhibitory inputs from other amacrine cells, but for most amacrine cells, little is known about the specificity and functional properties of their inhibitory inputs. Here, we have investigated GABAA receptors of the AII amacrine, a critical neuron in the rod pathway microcircuit, using patch-clamp recording in rat retinal slices. Puffer application of GABA evoked robust responses, but, surprisingly, spontaneous GABAA receptor-mediated postsynaptic currents were not observed, neither under control conditions nor following application of high-K+ solution to facilitate release. To investigate the biophysical and pharmacological properties of GABAA receptors in AIIs, we therefore used nucleated patches and a fast application system. Both brief and long pulses of GABA (3 mM) evoked GABAA receptor-mediated currents with slow, multi-exponential decay kinetics. The average weighted time constant (τw) of deactivation was ~163 ms. Desensitization was even slower, with τw ~330 ms. Non-stationary noise analysis of patch responses and directly observed channel gating yielded a single-channel conductance of ~23 pS. Pharmacological investigation suggested the presence of α2 and/or α3 subunits, as well as the γ2 subunit. Such subunit combinations are typical of GABAA receptors with slow kinetics. If synaptic GABAA receptors of AII amacrines have similar functional properties, the slow deactivation and desensitization kinetics will facilitate temporal summation of GABAergic inputs, allowing effective summation and synaptic integration to occur even for relatively low frequencies of inhibitory inputs.

During neuronal synaptic transmission, the exocytotic release of neurotransmitters from synaptic vesicles in the presynaptic neuron evokes a change in conductance for one or more types of ligand-gated ion channels in the postsynaptic neuron. The standard method of investigation uses electrophysiological recordings of the postsynaptic response. However, electrophysiological recordings can directly quantify the presynaptic release of neurotransmitters with high temporal resolution by measuring the membrane capacitance before and after exocytosis, as fusion of the membrane of presynaptic vesicles with the plasma membrane increases the total capacitance. While the standard technique for capacitance measurement assumes that the presynaptic cell is unbranched and can be represented as a simple resistance-capacitance (RC) circuit, neuronal exocytosis typically occurs at a distance from the soma. Even in such cases, however, it can be possible to detect a depolarization-evoked increase in capacitance. Here, we provide a detailed, step-by-step protocol that describes how "Sine + DC" (direct current) capacitance measurements can quantify the exocytotic release of neurotransmitters from AII amacrine cells in rat retinal slices. The AII is an important inhibitory interneuron of the mammalian retina that plays an important role in integrating rod and cone pathway signals. AII amacrines release glycine from their presynaptic dendrites, and capacitance measurements have been important for understanding the release properties of these dendrites. When the goal is to directly quantify the presynaptic release, there is currently no other competing method available. This protocol includes procedures for measuring depolarization-evoked exocytosis, using both standard square-wave pulses, arbitrary stimulus waveforms, and synaptic input. Key features • Quantification of exocytosis with the Sine + DC technique for visually targeted AII amacrines in retinal slices, using voltage-clamp and whole-cell patch-clamp recording. • Because exocytosis occurs away from the somatic recording electrode, the sine wave frequency must be lower than for the standard Sine + DC technique. • Because AII amacrines are electrically coupled, the sine wave frequency must be sufficiently high to avoid interference from other cells in the electrically coupled network. • The protocol includes procedures for measuring depolarization-evoked exocytosis using standard square-wave pulses, stimulation with arbitrary and prerecorded stimulus waveforms, and activation of synaptic inputs., Competing Interests: Competing interestsThe authors declare no competing interests., (©Copyright : © 2025 The Authors; This is an open access article under the CC BY license.)

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. Similarly, paired recordings reveal a dual-component EPSC with a slower sustained component that increases during development, even though the miniature EPSC (mEPSC) amplitude and kinetics do not change significantly. We thus propose that the readily releasable pool of vesicles from RBCs increases after eye opening, and we estimate that a short light flash can evoke the release of ∼4,000 vesicles onto a single mature AII-AC. [Display omitted] • The fast component of the light-evoked EPSC has a higher threshold than the slow component • Spontaneous mEPSC frequency increases with age, but amplitude and kinetics do not change • The EPSC charge in paired recordings increases with age and is highly temperature sensitive • Synaptic vesicle pool size and AMPA receptor desensitization both increase with age Kim et al. reveal that rod bipolar cell ribbon synapses undergo significant maturation after eye opening. The spontaneous mEPSC frequency, the dual-component EPSC charge transfer, and the peak amplitude of the slow component of the light-evoked EPSC all increase with age. [ABSTRACT FROM AUTHOR]