Marie L. Goeritz

Precise Temperature Compensation of Phase in a Rhythmic Motor Pattern

Computational modeling and experimentation in a model system for network dynamics reveal how network phase relationships are temperature-compensated in terms of their underlying synaptic and intrinsic membrane currents.

Robust circuit rhythms in small circuits arise from variable circuit components and mechanisms.

Small central pattern generating circuits found in invertebrates have significant advantages for the study of the circuit mechanisms that generate brain rhythms. Experimental and computational studies of small oscillatory circuits reveal that similar rhythms can arise from disparate mechanisms. Animal-to-animal variation in the properties of single neurons and synapses may underly robust circuit performance, and can be revealed by perturbations. Neuromodulation can produce altered circuit performance but also ensure reliable circuit function.

Distribution and physiological effects of B-type allatostatins (myoinhibitory peptides, MIPs) in the stomatogastric nervous system of the crab Cancer borealis.

The crustacean stomatogastric ganglion (STG) is modulated by a large number of amines and neuropeptides that are found in descending pathways from anterior ganglia or reach the STG via the hemolymph. Among these are the allatostatin (AST) B types, also known as myoinhibitory peptides (MIPs). We used mass spectrometry to determine the sequences of nine members of the AST‐B family of peptides that were found in the stomatogastric nervous system of the crab Cancer borealis. We raised an antibody against Cancer borealis allatostatin‐B1 (CbAST‐B1; VPNDWAHFRGSWa) and used it to map the distribution of CbAST‐B1‐like immunoreactivity (‐LI) in the stomatogastric nervous system. CbAST‐B1‐LI was found in neurons and neuropil in the commissural ganglia (CoGs), in somata in the esophageal ganglion (OG), in fibers in the stomatogastric nerve (stn), and in neuropilar processes in the STG. CbAST‐B1‐LI was blocked by preincubation with 10−6 M CbAST‐B1 and was partially blocked by lower concentrations. Electrophysiological recordings of the effects of CbAST‐B1, CbAST‐B2, and CbAST‐B3 on the pyloric rhythm of the STG showed that all three peptides inhibited the pyloric rhythm in a state‐dependent manner. Specifically, all three peptides at 10−8 M significantly decreased the frequency of the pyloric rhythm when the initial frequency of the pyloric rhythm was below 0.6 Hz. These data suggest important neuromodulatory roles for the CbAST‐B family in the stomatogastric nervous system. J. Comp. Neurol. 519:2658–2676, 2011.

Phase maintenance in a rhythmic motor pattern during temperature changes in vivo

Central-pattern-generating neural circuits function reliably throughout an animals life, despite constant molecular turnover and environmental perturbations. Fluctuations in temperature pose a problem to the nervous systems of poikilotherms because their body temperature follows the ambient temperature, thus affecting the temperature-dependent dynamics of various subcellular components that constitute neuronal circuits. In the crustacean stomatogastric nervous system, the pyloric circuit produces a triphasic rhythm comprising the output of the pyloric dilator, lateral pyloric, and pyloric constrictor neurons. In vitro, the phase relationships of these neurons are maintained over a fourfold change in pyloric frequency as temperature increases from 7°C to 23°C. To determine whether these temperature effects are also found in intact crabs, in the presence of sensory feedback and neuromodulator-rich environments, we measured the temperature dependence of the pyloric frequency and phases in vivo by implanting extracellular electrodes into Cancer borealis and Cancer pagurus and shifting tank water temperature from 11°C to 26°C. Pyloric frequency in the intact crab increased significantly with temperature (Q10 = 2-2.5), while pyloric phases were generally conserved. For a subset of the C. borealis experiments, animals were subsequently dissected and the stomatogastric ganglion subjected to a similar temperature ramp in vitro. We found that the maximal frequency attained at high temperatures in vivo is lower than it is under in vitro conditions. Our results demonstrate that, over a wide temperature range, the phases of the pyloric rhythm in vivo are generally preserved, but that the frequency range is more restricted than it is in vitro.

Localization and function of Ih channels in a small neural network.

Subthreshold ionic currents, which activate below the firing threshold and shape the cells firing properties, play important roles in shaping neural network activity. We examined the distribution and synaptic roles of the hyperpolarization-activated inward current (I(h)) in the pyloric network of the lobster stomatogastric ganglion (STG). I(h) channels are expressed throughout the STG in a patchy distribution and are highly expressed in the fine neuropil, an area that is rich in synaptic contacts. We performed double labeling for I(h) protein and for the presynaptic marker synaptotagmin. The large majority of labeling in the fine neuropil was adjacent but nonoverlapping, suggesting that I(h) is localized in close proximity to synapses but not in the presynaptic terminals. We compared the pattern of I(h) localization with Shal transient potassium channels, whose expression is coregulated with I(h) in many STG neurons. Unlike I(h), we found significant levels of Shal protein in the soma membrane and the primary neurite. Both proteins were found in the synaptic fine neuropil, but with little evidence of colocalization in individual neurites. We performed electrophysiological experiments to study a potential role for I(h) in regulating synaptic transmission. At a synapse between two identified pyloric neurons, the amplitude of inhibitory postsynaptic potentials (IPSPs) decreased with increasing postsynaptic activation of I(h). Pharmacological block of I(h) restored IPSP amplitudes to levels seen when I(h) was not activated. These experiments suggest that modulation of postsynaptic I(h) might play an important role in the control of synaptic strength in this rhythmogenic neural network.

Automatic parameter estimation of multicompartmental neuron models via minimization of trace error with control adjustment

We describe a new technique to fit conductance-based neuron models to intracellular voltage traces from isolated biological neurons. The biological neurons are recorded in current-clamp with pink (1/f) noise injected to perturb the activity of the neuron. The new algorithm finds a set of parameters that allows a multicompartmental model neuron to match the recorded voltage trace. Attempting to match a recorded voltage trace directly has a well-known problem: mismatch in the timing of action potentials between biological and model neuron is inevitable and results in poor phenomenological match between the model and data. Our approach avoids this by applying a weak control adjustment to the model to promote alignment during the fitting procedure. This approach is closely related to the control theoretic concept of a Luenberger observer. We tested this approach on synthetic data and on data recorded from an anterior gastric receptor neuron from the stomatogastric ganglion of the crab Cancer borealis. To test the flexibility of this approach, the synthetic data were constructed with conductance models that were different from the ones used in the fitting model. For both synthetic and biological data, the resultant models had good spike-timing accuracy.

Neuropilar Projections of the Anterior Gastric Receptor Neuron in the Stomatogastric Ganglion of the Jonah Crab, Cancer Borealis

Sensory neurons provide important feedback to pattern-generating motor systems. In the crustacean stomatogastric nervous system (STNS), feedback from the anterior gastric receptor (AGR), a muscle receptor neuron, shapes the activity of motor circuits in the stomatogastric ganglion (STG) via polysynaptic pathways involving anterior ganglia. The AGR soma is located in the dorsal ventricular nerve posterior to the STG and it has been thought that its axon passes through the STG without making contacts. Using high-resolution confocal microscopy with dye-filled neurons, we show here that AGR from the crab Cancer borealis also has local projections within the STG and that these projections form candidate contact sites with STG motor neurons or with descending input fibers from other ganglia. We develop and exploit a new masking method that allows us to potentially separate presynaptic and postsynaptic staining of synaptic markers. The AGR processes in the STG show diversity in shape, number of branches and branching structure. The number of AGR projections in the STG ranges from one to three simple to multiply branched processes. The projections come in close contact with gastric motor neurons and descending neurons and may also be electrically coupled to other neurons of the STNS. Thus, in addition to well described long-loop pathways, it is possible that AGR is involved in integration and pattern regulation directly in the STG.

How can motor systems retain performance over a wide temperature range? Lessons from the crustacean stomatogastric nervous system

Abstract Marine invertebrates, such as lobsters and crabs, deal with a widely and wildly fluctuating temperature environment. Here, we describe the effects of changing temperature on the motor patterns generated by the stomatogastric nervous system of the crab, Cancer borealis. Over a broad range of “permissive” temperatures, the pyloric rhythm increases in frequency but maintains its characteristic phase relationships. Nonetheless, at more extreme high temperatures, the normal triphasic pyloric rhythm breaks down, or “crashes”. We present both experimental and computational approaches to understanding the stability of both single neurons and networks to temperature perturbations, and discuss data that shows that the “crash” temperatures themselves may be environmentally regulated. These approaches provide insight into how the nervous system can be stable to a global perturbation, such as temperature, in spite of the fact that all biological processes are temperature dependent.

Sloppy morphological tuning in identified neurons of the crustacean stomatogastric ganglion

Neuronal physiology depends on a neuron’s ion channel composition and unique morphology. Variable ion channel compositions can produce similar neuronal physiologies across animals. Less is known regarding the morphological precision required to produce reliable neuronal physiology. Theoretical studies suggest that moraphology is tightly tuned to minimize wiring and conduction delay of synaptic events. We utilize high-resolution confocal microscopy and custom computational tools to characterize the morphologies of four neuron types in the stomatogastric ganglion (STG) of the crab Cancer borealis. Macroscopic branching patterns and fine cable properties are variable within and across neuron types. We compare these neuronal structures to synthetic minimal spanning neurite trees constrained by a wiring cost equation and find that STG neurons do not adhere to prevailing hypotheses regarding wiring optimization principles. In this highly modulated and oscillating circuit, neuronal structures appear to be governed by a space-filling mechanism that outweighs the cost of inefficient wiring. DOI: http://dx.doi.org/10.7554/eLife.22352.001