Spontaneous Oscillatory Activity of Starburst Amacrine Cells in the Mouse Retina

2005 ◽  
Vol 94 (3) ◽  
pp. 1770-1780 ◽  
Author(s):  
Jerome Petit-Jacques ◽  
Béla Völgyi ◽  
Bernardo Rudy ◽  
Stewart Bloomfield
Keyword(s):  
Feedback Inhibition ◽  
Glutamate Release ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Kainate Receptors ◽  
Oscillatory Activity ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Experimental Conditions ◽  
Starburst Amacrine Cells

Using patch-clamp techniques, we investigated the characteristics of the spontaneous oscillatory activity displayed by starburst amacrine cells in the mouse retina. At a holding potential of –70 mV, oscillations appeared as spontaneous, rhythmic inward currents with a frequency of ∼3.5 Hz and an average maximal amplitude of ∼120 pA. Application of TEA, a potassium channel blocker, increased the amplitude of oscillatory currents by >70% but reduced their frequency by ∼17%. The TEA effects did not appear to result from direct actions on starburst cells, but rather a modulation of their synaptic inputs. Oscillatory currents were inhibited by 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX), an antagonist of AMPA/kainate receptors, indicating that they were dependent on a periodic glutamatergic input likely from presynaptic bipolar cells. The oscillations were also inhibited by the calcium channel blockers cadmium and nifedipine, suggesting that the glutamate release was calcium dependent. Application of AP4, an agonist of mGluR6 receptors on on-center bipolar cells, blocked the oscillatory currents in starburst cells. However, application of TEA overcame the AP4 blockade, suggesting that the periodic glutamate release from bipolar cells is intrinsic to the inner plexiform layer in that, under experimental conditions, it can occur independent of photoreceptor input. The GABA receptor antagonists picrotoxin and bicuculline enhanced the amplitude of oscillations in starburst cells prestimulated with TEA. Our results suggest that this enhancement was due to a reduction of a GABAergic feedback inhibition from amacrine cells to bipolar cells and the resultant increased glutamate release. Finally, we found that some ganglion cells and other types of amacrine cell also displayed rhythmic activity, suggesting that oscillatory behavior is expressed by a number of inner retinal neurons.

Modulation of Excitatory Synaptic Transmission by GABAC Receptor-Mediated Feedback in the Mouse Inner Retina

2001 ◽  
Vol 86 (5) ◽  
pp. 2285-2298 ◽  
Author(s):  
Ko Matsui ◽  
Jun Hasegawa ◽  
Masao Tachibana
Keyword(s):  
Nmda Receptors ◽  
Time Course ◽  
Feedback Inhibition ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Mouse Retina ◽  
Receptor Subtypes ◽  
Inner Plexiform Layer ◽  
Cone Bipolar Cells

In many vertebrate CNS synapses, the neurotransmitter glutamate activates postsynaptic non- N-methyl-d-aspartate (NMDA) and NMDA receptors. Since their biophysical properties are quite different, the time course of excitatory postsynaptic currents (EPSCs) depends largely on the relative contribution of their activation. To investigate whether the activation of the two receptor subtypes is affected by the synaptic interaction in the inner plexiform layer (IPL) of the mouse retina, we analyzed the properties of the light-evoked responses ofon-cone bipolar cells and on-transient amacrine cells in a retinal slice preparation. on-transient amacrine cells were whole cell voltage-clamped, and the glutamatergic synaptic input from bipolar cells was isolated by a cocktail of pharmacological agents (bicuculline, strychnine, curare, and atropine). Direct puff application of NMDA revealed the presence of functional NMDA receptors. However, the light-evoked EPSC was not significantly affected byd(−)-2-amino-5-phosphonopentanoic acid (d-AP5), but suppressed by 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) or 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466). These results indicate that the light-evoked EPSC is mediated mainly by AMPA receptors under this condition. Since bipolar cells have GABACreceptors at their terminals, it has been suggested that bipolar cells receive feedback inhibition from amacrine cells. Application of (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA), a specific blocker of GABAC receptors, suppressed both the GABA-induced current and the light-evoked feedback inhibition observed in on-cone bipolar cells and enhanced the light-evoked EPSC of on-transient amacrine cells. In the presence of TPMPA, the light-evoked EPSC of amacrine cells was composed of AMPA and NMDA receptor-mediated components. Our results suggest that photoresponses of on-transient amacrine cells in the mouse retina are modified by the activation of presynaptic GABAC receptors, which may control the extent of glutamate spillover.

scholarly journals Bistratified starburst amacrine cells in Sox2 conditional knockout mouse retina display ON and OFF responses

2018 ◽  
Vol 120 (4) ◽  
pp. 2121-2129 ◽  
Author(s):  
Todd L. Stincic ◽  
Patrick W. Keeley ◽  
Benjamin E. Reese ◽  
W. Rowland Taylor
Keyword(s):  
Transcription Factor ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Conditional Knockout ◽  
Physiological Data ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Environmental Signals ◽  
Starburst Amacrine Cells

Cell-intrinsic factors, in conjunction with environmental signals, guide migration, differentiation, and connectivity during early development of neuronal circuits. Within the retina, inhibitory starburst amacrine cells (SBACs) comprise ON types with somas in the ganglion cell layer (GCL) and dendrites stratifying narrowly in the inner half of the inner plexiform layer (IPL) and OFF types with somas in the inner nuclear layer (INL) and dendrites stratifying narrowly in the outer half of the IPL. The transcription factor Sox2 is crucial to this subtype specification. Without Sox2, many ON-type SBACs destined for the GCL settle in the INL while many that reach the GCL develop bistratified dendritic arbors. This study asked whether ON-type SBACs in Sox2-conditional knockout retinas exhibit selective connectivity only with ON-type bipolar cells or their bistratified morphology allows them to connect to both ON and OFF bipolar cells. Physiological data demonstrate that these cells receive ON and OFF excitatory inputs, indicating that the ectopically stratified dendrites make functional synapses with bipolar cells. The excitatory inputs were smaller and more transient in Sox2-conditional knockout compared with wild type; however, inhibitory inputs appeared largely unchanged. Thus dendritic stratification, rather than cellular identification, may be the major factor that determines ON vs. OFF connectivity. NEW & NOTEWORTHY Conditional knockout of the transcription factor Sox2 during early embryogenesis converts a monostratifying starburst amacrine cell into a bistratifying starburst cell. Here we show that these bistratifying starburst amacrine cells form functional synaptic connections with both ON and OFF bipolar cells. This suggests that normal ON vs. OFF starburst connectivity may not require distinct molecular specification. Proximity alone may be sufficient to allow formation of functional synapses.

scholarly journals Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Thomas A Ray ◽  
Suva Roy ◽  
Christopher Kozlowski ◽  
Jingjing Wang ◽  
Jon Cafaro ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Surface Protein ◽  
Amacrine Cells ◽  
Direction Selectivity ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Starburst Amacrine Cells ◽  
Developing Neurons

A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here, we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism’s importance in forming circuit-specific sublayers.

scholarly journals Receptive field properties of bipolar cell axon terminals in direction-selective sublaminas of the mouse retina

2014 ◽  
Vol 112 (8) ◽  
pp. 1950-1962 ◽  
Author(s):  
Minggang Chen ◽  
Seunghoon Lee ◽  
Silvia J. H. Park ◽  
Loren L. Looger ◽  
Z. Jimmy Zhou
Keyword(s):  
Receptive Field ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Direction Selectivity ◽  
Bipolar Cells ◽  
Visual Signals ◽  
Mouse Retina ◽  
Patch Clamp Recording ◽  
Axon Terminals ◽  
Starburst Amacrine Cells

Retinal bipolar cells (BCs) transmit visual signals in parallel channels from the outer to the inner retina, where they provide glutamatergic inputs to specific networks of amacrine and ganglion cells. Intricate network computation at BC axon terminals has been proposed as a mechanism for complex network computation, such as direction selectivity, but direct knowledge of the receptive field property and the synaptic connectivity of the axon terminals of various BC types is required in order to understand the role of axonal computation by BCs. The present study tested the essential assumptions of the presynaptic model of direction selectivity at axon terminals of three functionally distinct BC types that ramify in the direction-selective strata of the mouse retina. Results from two-photon Ca2+ imaging, optogenetic stimulation, and dual patch-clamp recording demonstrated that 1) CB5 cells do not receive fast GABAergic synaptic feedback from starburst amacrine cells (SACs); 2) light-evoked and spontaneous Ca2+ responses are well coordinated among various local regions of CB5 axon terminals; 3) CB5 axon terminals are not directionally selective; 4) CB5 cells consist of two novel functional subtypes with distinct receptive field structures; 5) CB7 cells provide direct excitatory synaptic inputs to, but receive no direct GABAergic synaptic feedback from, SACs; and 6) CB7 axon terminals are not directionally selective, either. These findings help to simplify models of direction selectivity by ruling out complex computation at BC terminals. They also show that CB5 comprises two functional subclasses of BCs.

scholarly journals Evidence for novel transient clusters of cholinergic ganglion cells in the neonatal mouse retina

2019 ◽  
Author(s):  
Jean de Montigny ◽  
Vidhyasankar Krishnamoorthy ◽  
Fernando Rozenblit ◽  
Tim Gollisch ◽  
Evelyne Sernagor
Keyword(s):  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Neonatal Mouse ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Electrical Imaging ◽  
Subplate Neurons ◽  
Starburst Amacrine Cells ◽  
Cholinergic Cell

AbstractWaves of spontaneous activity sweep across the neonatal mouse retinal ganglion cell (RGC) layer, driven by directly interconnected cholinergic starburst amacrine cells (the only known retinal cholinergic cells) from postnatal day (P) 0-10, followed by waves driven by glutamatergic bipolar cells. We found transient clusters of cholinergic RGC-like cells around the optic disc during the period of cholinergic waves. They migrate towards the periphery between P2-9 and then they disappear. Pan-retinal multielectrode array recordings reveal that cholinergic wave origins follow a similar developmental center-to-periphery pattern. Electrical imaging unmasks hotspots of dipole electrical activity occurring in the vicinity of wave origins. We propose that these activity hotspots are sites for wave initiation and are related to the cholinergic cell clusters, reminiscent of activity in transient subplate neurons in the developing cortex, suggesting a universal hyper-excitability mechanism in developing CNS networks during the critical period for brain wiring.

scholarly journals Synaptic Regulation of the Light-Dependent Oscillatory Currents in Starburst Amacrine Cells of the Mouse Retina

2008 ◽  
Vol 100 (2) ◽  
pp. 993-1006 ◽  
Author(s):  
Jerome Petit-Jacques ◽  
Stewart A. Bloomfield
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Light Stimulus ◽  
Amacrine Cells ◽  
Kainate Receptors ◽  
Mouse Retina ◽  
Light Responses ◽  
Axon Terminals ◽  
Oscillatory Component ◽  
Starburst Amacrine Cells ◽  
Initial Peak

Responses of on-center starburst amacrine cells to steady light stimuli were recorded in the dark-adapted mouse retina. The response to spots of dim white light appear to show two components, an initial peak that correspond to the onset of the light stimulus and a series of oscillations that ride on top of the initial peak relaxation. The frequency of oscillations during light stimulation was three time higher than the frequency of spontaneous oscillations recorded in the dark. The light-evoked responses in starburst cells were exclusively dependent on the release of glutamate likely from presynaptic bipolar axon terminals and the binding of glutamate to AMPA/kainate receptors because they were blocked by 6-cyano-7-nitroquinoxalene-2,3-dione. The synaptic pathway responsible for the light responses was blocked by AP4, an agonist of metabotropic glutamate receptors that hyperpolarize on-center bipolar cells on activation. Light responses were inhibited by the calcium channel blockers cadmium ions and nifedipine, suggesting that the release of glutamate was calcium dependent. The oscillatory component of the response was specifically inhibited by blocking the glutamate transporter with d-threo-β-benzyloxyaspartic acid, suggesting that glutamate reuptake is necessary for the oscillatory release. GABAergic antagonists bicuculline, SR 95531, and picrotoxin increased the amplitude of the initial peak while they inhibit the frequency of oscillations. TTX had a similar effect. Strychnine, the blocker of glycine receptors did not affect the initial peak but strongly decreased the oscillations frequency. These inhibitory inputs onto the bipolar axon terminals shape and synchronize the oscillatory component.

Spontaneous oscillatory activity in rd1 mouse retina is transferred from ON pathway to OFF pathway via glycinergic synapse

2015 ◽  
Vol 113 (2) ◽  
pp. 420-425 ◽  
Author(s):  
Deepak Poria ◽  
Narender K. Dhingra
Keyword(s):  
Glycine Receptor ◽  
Plexiform Layer ◽  
Experimental Treatment ◽  
Amacrine Cells ◽  
Oscillatory Activity ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Aii Amacrine Cells ◽  
Rd1 Mouse ◽  
Aii Amacrine

Retinal ganglion cells (RGCs) spike randomly in the dark and carry information about visual stimuli to the brain via specific spike patterns. However, following photoreceptor loss, both ON and OFF type of RGCs exhibit spontaneous oscillatory spike activity, which reduces the quality of information they can carry. Furthermore, it is not clear how the oscillatory activity would interact with the experimental treatment approaches designed to produce artificial vision. The oscillatory activity is considered to originate in ON-cone bipolar cells, AII amacrine cells, and/or their synaptic interactions. However, it is unknown how the oscillatory activity is generated in OFF RGCs. We tested the hypothesis that oscillatory activity is transferred from the ON pathway to the OFF pathway via the glycinergic AII amacrine cells. Using extracellular loose-patch and whole cell patch recordings, we recorded oscillatory activity in ON and OFF RGCs and studied their response to strychnine, a specific glycine receptor blocker. The cells were labeled with a fluorescent dye, and their dendritic stratification in inner plexiform layer was studied using confocal microscopy. Application of strychnine resulted in abolition of the oscillatory burst activity in OFF RGCs but not in ON RGCs, implying that oscillatory activity is generated in ON pathway and is transferred to OFF pathway, likely via the glycinergic AII amacrine cells. We found oscillatory activity in RGCs as early as postnatal day 12 in rd1 mouse, when rod degeneration has started but cones are still intact. This suggests that the oscillatory activity in rd1 mouse retina originates in rod pathway.

Distribution of GABA immunoreactivity in the cat retina: A light- and electron-microscopic study

1989 ◽  
Vol 2 (5) ◽  
pp. 425-435 ◽  
Author(s):  
Roberta G. Pourcho ◽  
Michael T. Owczarzak
Keyword(s):  
Ganglion Cells ◽  
Feedback Inhibition ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Electron Microscopic ◽  
Cat Retina ◽  
Plexiform Layers ◽  
Major Target

AbstractThe distribution of GABA-like immunoreactivity in the cat retina was studied through the use of preembedding immunocytochemistry for light microscopy and by postembedding immunogold techniques for electron microscopy. Staining was observed in both inner and outer plexiform layers. Approximately 30% of the somata in the amacrine portion of the inner nuclear layer were immunoreactive and included amacrine and interplexiform cells. Horizontal cells and a subpopulation of cone bipolar cells were also stained. In the ganglion cell layer, staining was observed in both small- and medium-sized neurons. GABA-labeled amacrine cells were presynaptic to somata of amacrine cells and to dendrites of amacrine, bipolar, and ganglion cells. Bipolar cells were a major target, receiving more than 60% of all labeled synapses in the inner plexiform layer. Many of these contacts were reciprocal synapses. These findings support a major role for GABA-labeled amacrines in providing feedback inhibition to bipolar cells in the inner retina.

Characterization of inhibitory postsynaptic currents in rod bipolar cells of the mouse retina

2004 ◽  
Vol 21 (4) ◽  
pp. 645-652 ◽  
Author(s):  
MORITZ J. FRECH ◽  
KURT H. BACKUS
Keyword(s):  
Glutamate Release ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Synaptic Activity ◽  
Peak Amplitude ◽  
Mouse Retina ◽  
Decay Kinetics ◽  
Patch Clamp Technique ◽  
Postsynaptic Currents ◽  
Rod Bipolar Cells

The synaptic terminals of mammalian rod bipolar cells are the targets of multiple presynaptic inhibitory inputs arriving from glycinergic and GABAergic amacrine cells. To investigate the contribution of these different inhibitory receptor types, we have applied the patch-clamp technique in acutely isolated slices of the adult mouse retina. By using the whole-cell configuration, we measured and analyzed the spontaneous postsynaptic currents (PSCs) in rod bipolar cells. The spontaneous synaptic activity of rod bipolar cells was very low. However, when amacrine cells were depolarized by AMPA or kainate, the PSC frequency in rod bipolar cells increased significantly. These PSCs comprised several types that could be distinguished by pharmacological and kinetic criteria. Strychnine-sensitive, glycinergic PSCs were characterized by a mean peak amplitude of −43.5 pA and a weighted decay time constant (τw) of 10.9 ms. PSCs that persisted in the presence of strychnine, but were completely inhibited by bicuculline, were mediated by GABAARs. They had a mean peak amplitude of −20.0 pA and a significantly faster τwof 5.8 ms. Few PSCs remained in the presence of strychnine and bicuculline, suggesting that they were mediated by GABACRs. These PSCs were characterized by much smaller amplitudes (−6.2 pA) and a significantly slower decay kinetics (τw= 51.0 ms). We conclude that rod bipolar cells express at least three types of functionally different inhibitory receptors, namely GABAARs, GABACRs, and GlyRs that may ultimately regulate the Ca2+influx into rod bipolar cell terminals, thereby modulating their glutamate release.

scholarly journals Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

2017 ◽  
Author(s):  
Thomas A. Ray ◽  
Suva Roy ◽  
Christopher Kozlowski ◽  
Jingjing Wang ◽  
Jon Cafaro ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Surface Protein ◽  
Amacrine Cells ◽  
Direction Selectivity ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Starburst Amacrine Cells ◽  
Developing Neurons

Impact statementSelective synapse formation in a retinal motion-sensitive circuit is orchestrated by starburst amacrine cells, which use homotypic interactions to initiate formation of a dendritic scaffold that recruits projections from circuit partners.SUMMARYA common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially-migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism’s importance in forming circuit-specific sublayers.

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