The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 5, 2015
Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes se... more Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propa...
Neuronal communication relies on chemical synaptic transmission for information transfer and proc... more Neuronal communication relies on chemical synaptic transmission for information transfer and processing. Chemical neurotransmission is initiated by synaptic vesicle fusion with the presynaptic active zone resulting in release of neurotransmitters. Classical models have assumed that all synaptic vesicles within a synapse have the same potential to fuse under different functional contexts. In this model, functional differences among synaptic vesicle populations are ascribed to their spatial distribution in the synapse with respect to the active zone. Emerging evidence suggests, however, that synaptic vesicles are not a homogenous population of organelles, and they possess intrinsic molecular differences and differential interaction partners. Recent studies have reported a diverse array of synaptic molecules that selectively regulate synaptic vesicles' ability to fuse synchronously and asynchronously in response to action potentials or spontaneously irrespective of action potential...
Synapses represent the main junctures of communication between neurons in the nervous system. In ... more Synapses represent the main junctures of communication between neurons in the nervous system. In many neurotransmitter systems, a fraction of presynaptic terminals fails to release vesicles in response to action potential stimulation and strong calcium influx. These silent presynaptic terminals exhibit a reversible functional dormancy beyond low vesicle release probability, and dormancy status may have important implications in neural function. Recent advances have implicated presynaptic proteins interacting with vesicles downstream of cAMP and protein kinase A signaling cascades in modulating the number of these mute presynaptic terminals, and dormancy induction may represent a homeostatic neuroprotective mechanism active during pathological insults involving excitotoxicity. Interestingly, dormancy reversal may also be induced during Hebbian plasticity. Here, details of synaptic dormancy, recent insights into the molecular signaling cascades involved, and potential clinical and mechanistic implications of this form of synaptic plasticity are described.
Neuromodulation is well known to provide plasticity in pattern generating circuits, but few detai... more Neuromodulation is well known to provide plasticity in pattern generating circuits, but few details are available concerning modulation of motor pattern coordination. We are using the crustacean stomatogastric nervous system to examine how co-expressed rhythms are modulated to regulate frequency and maintain coordination. The system produces two related motor patterns, the gastric mill rhythm that regulates protraction and retraction of the teeth and the pyloric rhythm that filters food. These rhythms have different frequencies and are controlled by distinct mechanisms, but each circuit influences the rhythm frequency of the other via identified synaptic pathways. A projection neuron, MCN1, activates distinct versions of the rhythms, and we show that hormonal dopamine concentrations modulate the MCN1 elicited rhythm frequencies. Gastric mill circuit interactions with the pyloric circuit lead to changes in pyloric rhythm frequency that depend on gastric mill rhythm phase. Dopamine increases pyloric frequency during the gastric mill rhythm retraction phase. Higher gastric mill rhythm frequencies are associated with higher pyloric rhythm frequencies during retraction. However, dopamine slows the gastric mill rhythm frequency despite the increase in pyloric frequency. Dopamine reduces pyloric circuit influences on the gastric mill rhythm and upregulates activity in a gastric mill neuron, DG. Strengthened DG activity slows the gastric mill rhythm frequency and effectively reduces pyloric circuit influences, thus changing the frequency relationship between the rhythms. Overall dopamine shifts dependence of frequency regulation from intercircuit interactions to increased reliance on intracircuit mechanisms.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 5, 2015
Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes se... more Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propa...
Neuronal communication relies on chemical synaptic transmission for information transfer and proc... more Neuronal communication relies on chemical synaptic transmission for information transfer and processing. Chemical neurotransmission is initiated by synaptic vesicle fusion with the presynaptic active zone resulting in release of neurotransmitters. Classical models have assumed that all synaptic vesicles within a synapse have the same potential to fuse under different functional contexts. In this model, functional differences among synaptic vesicle populations are ascribed to their spatial distribution in the synapse with respect to the active zone. Emerging evidence suggests, however, that synaptic vesicles are not a homogenous population of organelles, and they possess intrinsic molecular differences and differential interaction partners. Recent studies have reported a diverse array of synaptic molecules that selectively regulate synaptic vesicles' ability to fuse synchronously and asynchronously in response to action potentials or spontaneously irrespective of action potential...
Synapses represent the main junctures of communication between neurons in the nervous system. In ... more Synapses represent the main junctures of communication between neurons in the nervous system. In many neurotransmitter systems, a fraction of presynaptic terminals fails to release vesicles in response to action potential stimulation and strong calcium influx. These silent presynaptic terminals exhibit a reversible functional dormancy beyond low vesicle release probability, and dormancy status may have important implications in neural function. Recent advances have implicated presynaptic proteins interacting with vesicles downstream of cAMP and protein kinase A signaling cascades in modulating the number of these mute presynaptic terminals, and dormancy induction may represent a homeostatic neuroprotective mechanism active during pathological insults involving excitotoxicity. Interestingly, dormancy reversal may also be induced during Hebbian plasticity. Here, details of synaptic dormancy, recent insights into the molecular signaling cascades involved, and potential clinical and mechanistic implications of this form of synaptic plasticity are described.
Neuromodulation is well known to provide plasticity in pattern generating circuits, but few detai... more Neuromodulation is well known to provide plasticity in pattern generating circuits, but few details are available concerning modulation of motor pattern coordination. We are using the crustacean stomatogastric nervous system to examine how co-expressed rhythms are modulated to regulate frequency and maintain coordination. The system produces two related motor patterns, the gastric mill rhythm that regulates protraction and retraction of the teeth and the pyloric rhythm that filters food. These rhythms have different frequencies and are controlled by distinct mechanisms, but each circuit influences the rhythm frequency of the other via identified synaptic pathways. A projection neuron, MCN1, activates distinct versions of the rhythms, and we show that hormonal dopamine concentrations modulate the MCN1 elicited rhythm frequencies. Gastric mill circuit interactions with the pyloric circuit lead to changes in pyloric rhythm frequency that depend on gastric mill rhythm phase. Dopamine increases pyloric frequency during the gastric mill rhythm retraction phase. Higher gastric mill rhythm frequencies are associated with higher pyloric rhythm frequencies during retraction. However, dopamine slows the gastric mill rhythm frequency despite the increase in pyloric frequency. Dopamine reduces pyloric circuit influences on the gastric mill rhythm and upregulates activity in a gastric mill neuron, DG. Strengthened DG activity slows the gastric mill rhythm frequency and effectively reduces pyloric circuit influences, thus changing the frequency relationship between the rhythms. Overall dopamine shifts dependence of frequency regulation from intercircuit interactions to increased reliance on intracircuit mechanisms.
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Papers by Devon Crawford