Illuminating the Multifaceted Roles of Neurotransmission in Shaping Neuronal Circuitry

Okawa, Haruhisa; Hoon, Mrinalini; Yoshimatsu, Takeshi; Santina, Luca Della; Wong, Rachel

doi:10.1016/j.neuron.2014.08.029

Cited by 38 publications

(28 citation statements)

References 147 publications

(236 reference statements)

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“…This mechanism of partner switching that would not be possible through local zone wandering [28–30] allows the cell population to test different conflicting mating configurations (reminiscent of the configurations of frustrated physical systems with quenched disorder [42]). This non-deterministic conceptual pairing framework may be valid beyond yeast sex, for instance for the formation of connections in filamentous fungal mycelia [43] or for activity-dependent stabilization of neuronal connections [44]. …”

Section: Resultsmentioning

confidence: 99%

Local Pheromone Release from Dynamic Polarity Sites Underlies Cell-Cell Pairing during Yeast Mating

et al. 2016

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Summary Cell pairing is central for many processes, including immune defense, neuronal connection, hyphal fusion or sexual reproduction. How does a cell orient towards a partner, especially when faced with multiple choices? Fission yeast Schizosaccharomyces pombe P- and M-cells, which respectively express P- and M-factor pheromones [1, 2], pair during the mating process induced by nitrogen starvation. Engagement of pheromone receptors Map3 and Mam2 [3, 4] with their cognate pheromone ligands leads to activation of the Gα-protein Gpa1 to signal sexual differentiation [3, 5, 6]. Prior to cell pairing, the Cdc42 GTPase, a central regulator of cell polarization, forms dynamic zones of activity at the cell periphery at distinct locations over time [7]. Here, we show that Cdc42-GTP polarization sites contain the M-factor transporter Mam1, the general secretion machinery, which underlies P-factor secretion, and Gpa1, suggesting these are sub-cellular zones of pheromone secretion and signaling. Zone lifetimes scale with pheromone concentration. Computational simulations of pair formation through a fluctuating zone show that the combination of local pheromone release and sensing, short pheromone decay length, and pheromone-dependent zone stabilization leads to efficient pair formation. Consistently, pairing efficiency is reduced in absence of the P-factor protease. Similarly, zone stabilization at reduced pheromone levels, which occurs in absence of the predicted GTPase-activating protein for Ras, leads to reduction in pairing efficiency. We propose that efficient cell pairing relies on a fluctuating local signal emission and perception, which become locked into place through stimulation.

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Section: Resultsmentioning

confidence: 99%

Local Pheromone Release from Dynamic Polarity Sites Underlies Cell-Cell Pairing during Yeast Mating

et al. 2016

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“…The finding that the state of sensory transmitter release sets the synaptic density of a defined class of sensory-motor connections brings proprioceptive sensory neurons into the general fold of activity-dependent circuit refinement that operates elsewhere in the central nervous system (CNS) (Okawa et al, 2014). In other circuits for instance, presynaptic activity drives the competitive elimination of motor synapses from multiply innervated muscle fibers and the elimination of supernumerary climbing fibers from cerebellar Purkinje neurons (Buffelli et al, 2003; Lorenzetto et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…The set of potential postsynaptic motor neuron partners that serve as substrates for pruning can be independently identified by their molecular identity and connectivity. In nearly all other regions of the CNS, target neurons are perceived as molecularly and functionally equivalent at the time of activity-driven pruning (Okawa et al, 2014). As a consequence, analysis of the sensory-motor system permits a separation of the contribution of sensory activity to the formation of selective sensory connections with distinct motor targets and the subsequent refinement of connection densities.…”

Section: Discussionmentioning

confidence: 99%

Activity Regulates the Incidence of Heteronymous Sensory-Motor Connections

Mendelsohn

Simon

Abbott

et al. 2015

Neuron

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Summary The construction of spinal sensory-motor circuits involves the selection of appropriate synaptic partners and the allocation of precise synaptic input densities. Many aspects of spinal sensory-motor selectivity appear to be preserved when peripheral sensory activation is blocked, which has led to a view that sensory-motor circuits are assembled in an activity-independent manner. Yet it remains unclear whether activity-dependent refinement has a role in the establishment of connections between sensory afferents and those motor pools that have synergistic biomechanical functions. We show here that genetically abolishing central sensory-motor neurotransmission leads to a selective enhancement in the number and density of such “heteronymous” connections, whereas other aspects of sensory-motor connectivity are preserved. Spike-timing dependent synaptic refinement represents one possible mechanism for the changes in connectivity observed after activity blockade. Our findings therefore reveal that sensory activity does have a limited and selective role in the establishment of patterned monosynaptic sensory-motor connections.

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“…Rather, the reader is referred to excellent, recent reviews of these topics (Blankenship & Feller 2010, Okawa et al 2014, Do & Yau 2010, LeGates et al 2014). …”

Section: Introductionmentioning

confidence: 99%

Functional Circuitry of the Retina

Demb

Singer

2015

Annu. Rev. Vis. Sci.

167

131

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The mammalian retina is an important model system for studying neural circuitry: Its role in sensation is clear, its cell types are relatively well defined, and its responses to natural stimuli—light patterns—can be studied in vitro. To solve the retina, we need to understand how the circuits pre-synaptic to its output neurons, ganglion cells, divide the visual scene into parallel representations to be assembled and interpreted by the brain. This requires identifying the component interneurons and understanding how their intrinsic properties and synapses generate circuit behaviors. Because the cellular composition and fundamental properties of the retina are shared across species, basic mechanisms studied in the genetically modifiable mouse retina apply to primate vision. We propose that the apparent complexity of retinal computation derives from a straightforward mechanism—a dynamic balance of synaptic excitation and inhibition regulated by use-dependent synaptic depression—applied differentially to the parallel pathways that feed ganglion cells.

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Illuminating the Multifaceted Roles of Neurotransmission in Shaping Neuronal Circuitry

Cited by 38 publications

References 147 publications

Local Pheromone Release from Dynamic Polarity Sites Underlies Cell-Cell Pairing during Yeast Mating

Local Pheromone Release from Dynamic Polarity Sites Underlies Cell-Cell Pairing during Yeast Mating

Activity Regulates the Incidence of Heteronymous Sensory-Motor Connections

Functional Circuitry of the Retina

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