Biology subjects

Simmers, J.

Publications and source records attributed to Simmers, J..

5 recordsLinked to original sources

bioRxiv2026

Frequency modulation of organelle calcium-dependent voltage oscillations: an essential memory trace produced by operant conditioning in Aplysia

Spontaneous voltage oscillations in neuronal ensembles play a critical role in memory formation and storage. Although oscillatory activities arising endogenously within central pattern-generating (CPG) networks underlie many rhythmic motor behaviors, the contribution of such autonomous signals to motor learning and memory remains poorly understood. Previously, we found that the buccal CPG network driving food-seeking behavior in Aplysia contains a subset of electrically-coupled neurons that produces spontaneous, variable-amplitude voltage oscillations instigating infrequent and irregular cycles of patterned motor output. This pattern-initiating activity originates from organelle-derived, inositol triphosphate (IP3) receptor-dependent calcium oscillations in a pair of identified decision-making neurons (B63) within the CPG subset (Bedecarrats et al., 2021). Here, we show that the cycle frequency of this spontaneous pacemaker mechanism based on intracellular calcium store release is persistently increased by operant reward-learning, and in association with increased B63 excitability, constitutes a fundamental memory trace for accelerated and stereotyped rhythmic food-seeking movements. eLife AssessmentSlow voltage oscillations in neuronal ensembles can contribute to learning and memory. This study identifies long-lasting plasticity in the dynamics of oscillatory intracellular calcium store release in key neurons of Aplysias food-seeking network, serving as a sub-cellular substrate for operant-reward learning that leads to the rhythmic expression of motor output producing compulsive-like behavior.

neuroscience↗

bioRxiv2023

Sodium-mediated plateau potentials in an identified decisional neuron contribute to feeding-related motor pattern genesis in Aplysia

Motivated behaviors such as feeding depend on the functional properties of decision neurons which provide the flexibility required for behavioral adaptation. Here, we analyzed the ionic basis of the endogenous membrane properties of an identified decision neuron (B63) that drive radula biting cycles underlying food-seeking behavior in Aplysia. Each spontaneous bite cycle arises from the irregular triggering of a plateau-like potential and resultant bursting by rhythmic subthreshold oscillations in B63s membrane potential. In isolated buccal ganglion preparations, and after synaptic isolation, the expression of B63s plateau potentials persisted after removal of extracellular calcium, but was completely suppressed in a TTX-containing bath solution, thereby indicating the contribution of a transmembrane Na+ influx. Potassium outward efflux through TEA- and calcium-sensitive channels was found to contribute to each plateaus active termination. This intrinsic plateauing capability, in contrast to B63s membrane potential oscillation, was blocked by the ICAN blocker flufenamic acid (FFA). Conversely, the SERCA blocker cyclopianozic acid (CPA), which abolished the neurons oscillation, did not prevent the expression of experimentally evoked-plateau potentials. These results therefore indicate that the dynamic properties of the decision neuron B63 rely on two distinct mechanisms involving different sub-populations of ionic conductances. NEW & NOTEWORTHYHere, we report an endogenous plateau property underlying bursting in a bilateral pair of buccal ganglion pacemaker neurons (B63) which trigger individual motor pattern cycles for food-seeking behavior in the marine mollusk Aplysia. The ionic mechanisms of this membrane bistability in B63 rely critically on voltage-dependent sodium inward currents. The expression of these plateau properties and the underlying endogenous oscillatory pacemaker drive can be dissociated pharmacologically, indicating that the two intrinsic properties depend on different sets of conductances. Our results thus shed new light on the mechanisms of spontaneous decision making in Aplysia.

neuroscience↗

bioRxiv2022

Microglia shape the embryonic development of mammalian respiratory networks

Microglia, brain-resident macrophages, play key roles during prenatal development in defining neural circuitry function, including ensuring proper synaptic wiring and maintaining homeostasis. Mammalian breathing rhythmogenesis arises from interacting brainstem neural networks that are assembled during embryonic development, but the specific role of microglia in this process remains unknown. Here, we investigated the anatomical and functional consequences of respiratory circuit formation in the absence of microglia. We first established the normal distribution of microglia within the wild-type (WT, Pu.1+/+) mouse brainstem at embryonic ages when the respiratory networks are known to emerge (embryonic day (E) 14.5 for the parafacial respiratory group (epF) and E16.5 for the preBotzinger complex (preBotC)). In transgenic mice depleted of microglia (Pu.1-/- mutant), we performed anatomical staining, calcium imaging and electrophysiological recordings of neuronal activities in vitro to assess the status of these circuits at their respective times of functional emergence. Spontaneous respiratory-related activity recorded from reduced in vitro preparations showed an abnormally slow rhythm frequency expressed by the epF at E14.5, the preBotC at E16.5 and in the phrenic motor nerves from E16.5 onwards. These deficits were associated with a reduced number of active epF neurons, defects in commissural projections that couple the bilateral preBotC half-centers, and an accompanying decrease in their functional coordination. These abnormalities probably contribute to eventual neonatal death, since plethysmography revealed that E18.5 Pu.1-/- embryos are unable to sustain breathing activity ex utero. Our results thus point to a crucial contribution of microglia in the proper establishment of the central respiratory command during embryonic development.

neuroscience↗

bioRxiv2021

Organelle calcium-derived voltage oscillations in pacemaker neurons drive food-seeking behavior in Aplysia

The expression of motivated behaviors depends on both external and internally-arising neural stimuli, yet the intrinsic releasing mechanisms for such variably occurring behaviors remain elusive. In isolated nervous system preparations of Aplysia, we have found that irregularly expressed cycles of motor output underlying food-seeking behavior arise from regular membrane potential oscillations of varying magnitude in an identified pair of interneurons (B63) in the bilateral buccal ganglia. This rhythmic signal, which is endogenous and specific to the B63 cells, is generated by organelle-derived intracellular calcium fluxes that activate voltage-independent plasma membrane channels. The resulting voltage oscillation spreads throughout a subset of gap junction-coupled buccal network neurons and by triggering plateau potential-mediated bursts in B63, can initiate motor output driving food-seeking action. Thus, an atypical neuronal pacemaker mechanism, based on rhythmic intracellular calcium store release and intercellular propagation, can act as an autonomous intrinsic releaser for the occurrence of a motivated behavior.

neuroscience↗

bioRxiv2017

Functional limb muscle innervation prior to cholinergic transmitter specification during early metamorphosis in Xenopus

In vertebrates, functional motoneurons are defined as differentiated neurons that are connected to a central premotor network and activate peripheral muscle using acetylcholine. Generally, motoneurons and muscles develop simultaneously during embryogenesis. However, during Xenopus metamorphosis, developing limb motoneurons must reach their target muscles through the already established larval cholinergic axial neuromuscular system. Here, we demonstrate that at metamorphosis onset, spinal neurons retrogradely labeled from the emerging hindlimbs initially express neither choline acetyltransferase nor vesicular acetylcholine transporter. Nevertheless, they are positive for the motoneuronal transcription factor Islet1/2 and exhibit intrinsic and axial locomotor-driven electrophysiological activity. Moreover, the early appendicular motoneurons activate developing limb muscles via nicotinic antagonist-resistant, glutamate antagonist-sensitive, neuromuscular synapses. Coincidently, the hindlimb muscles transiently express glutamate, but not nicotinic receptors. Subsequently, both pre- and postsynaptic neuromuscular partners switch definitively to typical cholinergic transmitter signaling. Thus, our results demonstrate a novel context-dependent re-specification of neurotransmitter phenotype during neuromuscular system development.

neuroscience↗