näkemys - Computational neuroscience - # Mechanisms of Parallel Visual Processing in the Retina

Distinct Synaptic Mechanisms Underlying Transient and Sustained Signaling in Parallel ON Pathways of the Mouse Retina

Q: What other mechanisms, beyond differences in synaptic vesicle pool dynamics, might contribute to the generation of transient versus sustained responses in parallel ON pathways

In addition to differences in synaptic vesicle pool dynamics, several other mechanisms could contribute to the generation of transient versus sustained responses in parallel ON pathways. One potential factor is the differential expression of glutamate receptor subtypes on the postsynaptic RGCs. Variations in the composition of ionotropic glutamate receptors, such as AMPA and NMDA receptors, can influence the kinetics of excitatory postsynaptic currents and shape the temporal characteristics of the response. Moreover, the presence of metabotropic glutamate receptors (mGluRs) on RGC dendrites could modulate the kinetics of synaptic transmission by regulating intracellular signaling pathways. Another possible mechanism is the involvement of presynaptic modulatory factors that regulate neurotransmitter release. Neuromodulators, such as dopamine or acetylcholine, can modulate the release of glutamate from bipolar cell terminals and impact the temporal dynamics of synaptic transmission. These neuromodulatory signals can act on presynaptic receptors or intracellular signaling pathways to alter the release probability of synaptic vesicles and influence the kinetics of excitatory inputs to RGCs. Furthermore, the structural organization of the synaptic machinery at the bipolar cell terminals could play a role in determining the kinetics of glutamate release. Variations in the number and distribution of active zones, the presence of specialized proteins involved in vesicle fusion, or the efficiency of vesicle recycling mechanisms could all contribute to differences in the temporal profile of synaptic transmission between bipolar cell subtypes.

Q: How do the findings from this study on cone-mediated pathways relate to the mechanisms underlying transient and sustained responses in rod-mediated pathways in the retina

The findings from this study on cone-mediated pathways provide insights into the mechanisms underlying transient and sustained responses in rod-mediated pathways in the retina. While this study focused on the parallel ON pathways driven by cone photoreceptors, similar principles likely apply to the rod-mediated pathways that operate under dim light conditions. Rod bipolar cells, which transmit signals from rod photoreceptors to RGCs, are also known to exhibit transient or sustained response properties based on their synaptic inputs and intrinsic properties. In rod-mediated pathways, differences in the kinetics of glutamate release from rod bipolar cells could contribute to the generation of transient or sustained responses in downstream RGCs. Similar to cone bipolar cells, rod bipolar cells may exhibit subtype-specific differences in synaptic vesicle dynamics, ribbon size, or presynaptic modulation that shape the temporal characteristics of excitatory inputs to RGCs. Understanding the mechanisms that govern transient and sustained signaling in rod pathways could parallel the findings from cone pathways and provide a comprehensive view of how visual information is processed in the retina under different lighting conditions.

Q: Given the importance of parallel processing in the nervous system, to what extent do similar principles of signal diversification at the level of synaptic transmission apply in other sensory modalities or brain regions

The principles of signal diversification at the level of synaptic transmission observed in the retina's parallel ON pathways likely apply to other sensory modalities and brain regions where parallel processing is essential for information encoding. In various sensory systems, such as the auditory system, somatosensory system, and olfactory system, parallel pathways are responsible for processing distinct features of sensory stimuli. Similar to the retina, these sensory pathways likely exhibit differential response properties in parallel circuits to encode specific sensory attributes. Moreover, in higher brain regions involved in complex cognitive functions, such as the neocortex, parallel processing is crucial for integrating and processing diverse inputs to generate appropriate behavioral responses. The mechanisms identified in the retina, such as differences in synaptic vesicle dynamics, receptor expression, and presynaptic modulation, may also play a role in shaping the functional diversity of neural circuits in other brain regions. By understanding how parallel pathways generate distinct outputs from common inputs, researchers can gain valuable insights into the neural basis of sensory perception, cognition, and behavior.

Keskeiset käsitteet

Bipolar cell synapses are a primary site of divergence in kinetically distinct visual pathways, with differences in synaptic vesicle pool size and replenishment contributing to transient versus sustained excitatory input to ON-transient and ON-sustained retinal ganglion cells.

Tiivistelmä

The study examines the mechanisms underlying the generation of transient versus sustained responses in parallel ON pathways of the mouse retina. The authors directly compare the visual response properties of ON-transient (ON-T) and ON-sustained (ON-S) retinal ganglion cells (RGCs) with their presynaptic bipolar cell partners.

Key findings:

Bipolar cell subtypes that provide the major input to ON-T (type 5i) or ON-S RGCs (types 6 and 7) have indistinguishable light-evoked voltage responses, suggesting mechanisms downstream of bipolar cell voltage generation are responsible for the distinct kinetics of excitatory input to the RGC types.
Amacrine cell-mediated presynaptic inhibition does not contribute to the generation of transient versus sustained excitatory input to ON-T and ON-S RGCs.
Differences in the extent of stimulus-evoked vesicle pool depletion at bipolar cell synapses onto ON-T versus ON-S RGCs likely underlie the transient versus sustained excitatory input to these RGC types.
Bipolar cell subtype-specific differences in synaptic ribbon size and associated vesicle pool size may contribute to the distinct synaptic release properties.

The findings indicate that bipolar cell synapses are a primary site of divergence in kinetically distinct visual pathways in the retina, with differences in synaptic vesicle pool dynamics playing a key role.

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biorxiv.org

Tilastot

The average steady-state amplitude of light-evoked glutamate signals at ON-T RGC dendrites was 21 ± 13% of the peak amplitude, compared to 44 ± 12% at ON-S RGC dendrites.
At the shortest inter-flash interval tested (50 ms), the response to a second flash was almost completely suppressed in ON-T RGCs (paired flash ratio = 0.04 ± 0.01), whereas the response in ON-S RGCs was suppressed considerably less (paired flash ratio = 0.29 ± 0.04).
The synaptic ribbons in type 6 bipolar cells were approximately 2-3 fold larger than those in type 5i bipolar cells.

Lainaukset

"Bipolar cell synapses are a primary point of divergence in kinetically distinct visual pathways."
"Differences in the extent of stimulus-evoked vesicle pool depletion at bipolar cell synapses onto ON-T versus ON-S RGCs likely underlie the transient versus sustained excitatory input to these RGC types."
"Bipolar cell subtype-specific differences in synaptic ribbon size and associated vesicle pool size may contribute to the distinct synaptic release properties."

Tärkeimmät oivallukset

Cone bipolar cell synapses generate transient versus sustained signals in parallel ON pathways of the mouse retina

by Kuo,S. P., Y... klo www.biorxiv.org 05-14-2024

https://www.biorxiv.org/content/10.1101/2024.05.13.593825v1

Syvällisempiä Kysymyksiä

What other mechanisms, beyond differences in synaptic vesicle pool dynamics, might contribute to the generation of transient versus sustained responses in parallel ON pathways

In addition to differences in synaptic vesicle pool dynamics, several other mechanisms could contribute to the generation of transient versus sustained responses in parallel ON pathways. One potential factor is the differential expression of glutamate receptor subtypes on the postsynaptic RGCs. Variations in the composition of ionotropic glutamate receptors, such as AMPA and NMDA receptors, can influence the kinetics of excitatory postsynaptic currents and shape the temporal characteristics of the response. Moreover, the presence of metabotropic glutamate receptors (mGluRs) on RGC dendrites could modulate the kinetics of synaptic transmission by regulating intracellular signaling pathways.
Another possible mechanism is the involvement of presynaptic modulatory factors that regulate neurotransmitter release. Neuromodulators, such as dopamine or acetylcholine, can modulate the release of glutamate from bipolar cell terminals and impact the temporal dynamics of synaptic transmission. These neuromodulatory signals can act on presynaptic receptors or intracellular signaling pathways to alter the release probability of synaptic vesicles and influence the kinetics of excitatory inputs to RGCs.
Furthermore, the structural organization of the synaptic machinery at the bipolar cell terminals could play a role in determining the kinetics of glutamate release. Variations in the number and distribution of active zones, the presence of specialized proteins involved in vesicle fusion, or the efficiency of vesicle recycling mechanisms could all contribute to differences in the temporal profile of synaptic transmission between bipolar cell subtypes.

How do the findings from this study on cone-mediated pathways relate to the mechanisms underlying transient and sustained responses in rod-mediated pathways in the retina

The findings from this study on cone-mediated pathways provide insights into the mechanisms underlying transient and sustained responses in rod-mediated pathways in the retina. While this study focused on the parallel ON pathways driven by cone photoreceptors, similar principles likely apply to the rod-mediated pathways that operate under dim light conditions. Rod bipolar cells, which transmit signals from rod photoreceptors to RGCs, are also known to exhibit transient or sustained response properties based on their synaptic inputs and intrinsic properties.
In rod-mediated pathways, differences in the kinetics of glutamate release from rod bipolar cells could contribute to the generation of transient or sustained responses in downstream RGCs. Similar to cone bipolar cells, rod bipolar cells may exhibit subtype-specific differences in synaptic vesicle dynamics, ribbon size, or presynaptic modulation that shape the temporal characteristics of excitatory inputs to RGCs. Understanding the mechanisms that govern transient and sustained signaling in rod pathways could parallel the findings from cone pathways and provide a comprehensive view of how visual information is processed in the retina under different lighting conditions.

Given the importance of parallel processing in the nervous system, to what extent do similar principles of signal diversification at the level of synaptic transmission apply in other sensory modalities or brain regions

The principles of signal diversification at the level of synaptic transmission observed in the retina's parallel ON pathways likely apply to other sensory modalities and brain regions where parallel processing is essential for information encoding. In various sensory systems, such as the auditory system, somatosensory system, and olfactory system, parallel pathways are responsible for processing distinct features of sensory stimuli. Similar to the retina, these sensory pathways likely exhibit differential response properties in parallel circuits to encode specific sensory attributes.
Moreover, in higher brain regions involved in complex cognitive functions, such as the neocortex, parallel processing is crucial for integrating and processing diverse inputs to generate appropriate behavioral responses. The mechanisms identified in the retina, such as differences in synaptic vesicle dynamics, receptor expression, and presynaptic modulation, may also play a role in shaping the functional diversity of neural circuits in other brain regions. By understanding how parallel pathways generate distinct outputs from common inputs, researchers can gain valuable insights into the neural basis of sensory perception, cognition, and behavior.