The legacies of A. O. Dennis Willows and Peter A. Getting: neuroscience research using .

This review was inspired by a January 2024 conference held at Friday Harbor Laboratories, WA, honoring the pioneering work of A.O. Dennis Willows, who initiated research on the sea slug (now ).

Surprising multifunctionality of a swim CPG neuron: C2 drives the early phase of postswim crawling despite being silent during the behavior.

In response to a suitably aversive skin stimulus, the marine mollusk launches an escape swim followed by several minutes of high-speed crawling. The two escape behaviors are highly dissimilar: whereas the swim is a muscular behavior involving alternating ventral and dorsal whole body flexions, the crawl is a nonrhythmic gliding behavior mediated by the beating of foot cilia. The serotonergic dorsal swim interneurons (DSIs) are members of the swim central pattern generator (CPG) and also strongly drive crawling.

Division of labor for defensive retaliation and preemption by the peripheral and central nervous systems in the nudibranch Berghia.

Relatively little is known about how peripheral nervous systems (PNSs) contribute to the patterning of behavior in which their role transcends the simple execution of central motor commands or mediation of reflexes. We sought to draw inferences to this end in the aeolid nudibranch Berghia stephanieae, which generates a rapid, dramatic defense behavior, "bristling." This behavior involves the coordinated movement of cerata, dozens of venomous appendages emerging from the animal's mantle.

Neural division of labor: the gastropod defends against attack using its PNS to retaliate and its CNS to erect a defensive screen.

Relatively little is known about how the peripheral nervous system (PNS) contributes to the patterning of behavior, in which its role transcends the simple execution of central motor commands or mediation of reflexes. We sought to draw inferences to this end in the aeolid nudibranch , which generates a rapid, dramatic defense behavior, "bristling." This behavior involves the coordinated movement of cerata, dozens of venomous appendages emerging from the animal's mantle.

Neuroethology: Generating complex behavioral sequences with distributed nerve nets.

How are animals equipped with only diffusely distributed nerve nets able to generate complex behaviors? A new study in Hydra vulgaris proposes that a peptide-based 'wireless connectome' works in concert with two familiar network-coordinating mechanisms to generate the animal's remarkable somersault behavior.

The Importance of Being Correlated: Implications of Dependence in Joint Spectral Inference across Multiple Networks.

Spectral inference on multiple networks is a rapidly-developing subfield of graph statistics. Recent work has demonstrated that joint, or simultaneous, spectral embedding of multiple independent networks can deliver more accurate estimation than individual spectral decompositions of those same networks. Such inference procedures typically rely heavily on independence assumptions across the multiple network realizations, and even in this case, little attention has been paid to the induced network correlation that can be a consequence of such joint embeddings.

Photodiode-Based Optical Imaging for Recording Network Dynamics with Single-Neuron Resolution in Non-Transgenic Invertebrates.

The development of transgenic invertebrate preparations in which the activity of specifiable sets of neurons can be recorded and manipulated with light represents a revolutionary advance for studies of the neural basis of behavior. However, a downside of this development is its tendency to focus investigators on a very small number of "designer" organisms (e.g.

Reduced presynaptic vesicle stores mediate cellular and network plasticity defects in an early-stage mouse model of Alzheimer's disease.

Background: Identifying effective strategies to prevent memory loss in AD has eluded researchers to date, and likely reflects insufficient understanding of early pathogenic mechanisms directly affecting memory encoding. As synaptic loss best correlates with memory loss in AD, refocusing efforts to identify factors driving synaptic impairments may provide the critical insight needed to advance the field. In this study, we reveal a previously undescribed cascade of events underlying pre and postsynaptic hippocampal signaling deficits linked to cognitive decline in AD.

An Argument for Amphetamine-Induced Hallucinations in an Invertebrate.

Hallucinations - compelling perceptions of stimuli that aren't really there - occur in many psychiatric and neurological disorders, and are triggered by certain drugs of abuse. Despite their clinical importance, the neuronal mechanisms giving rise to hallucinations are poorly understood, in large part due to the absence of animal models in which they can be induced, confirmed to be endogenously generated, and objectively analyzed. In humans, amphetamine (AMPH) and related psychostimulants taken in large or repeated doses can induce hallucinations.

Serial-section atlas of the Tritonia pedal ganglion.

The pedal ganglion of the nudibranch gastropod Tritonia diomedea has been the focus of neurophysiological studies for more than 50 yr. These investigations have examined the neural basis of behaviors as diverse as swimming, crawling, reflex withdrawals, orientation to water flow, orientation to the earth's magnetic field, and learning. Despite this sustained research focus, most studies have confined themselves to the layer of neurons that are visible on the ganglion surface, leaving many neurons, which reside in deeper layers, largely unknown and thus unstudied.

A spiral attractor network drives rhythmic locomotion.

The joint activity of neural populations is high dimensional and complex. One strategy for reaching a tractable understanding of circuit function is to seek the simplest dynamical system that can account for the population activity. By imaging 's pedal ganglion during fictive locomotion, here we show that its population-wide activity arises from a low-dimensional spiral attractor.

Watching a memory form-VSD imaging reveals a novel memory mechanism.

Studies of the mechanisms underlying memory formation have largely focused on the synapse. However, recent evidence suggests that additional, non-synaptic, mechanisms also play important roles in this process. We recently described a novel memory mechanism whereby a particular class of neurons was recruited into the escape swim network with sensitization, a non-associative form of learning.

Memory Formation in Tritonia via Recruitment of Variably Committed Neurons.

Prior studies have found that functional networks can rapidly add neurons as they build short-term memories, yet little is known about the principles underlying this process. Using voltage-sensitive dye imaging, we found that short-term sensitization of Tritonia's swim motor program involves rapid expansion of the number of participating neurons. Tracking neurons across trials revealed that this involves the conversion of recently discovered variably participating neurons to reliable status.

Modular deconstruction reveals the dynamical and physical building blocks of a locomotion motor program.

The neural substrates of motor programs are only well understood for small, dedicated circuits. Here we investigate how a motor program is constructed within a large network. We imaged populations of neurons in the Aplysia pedal ganglion during execution of a locomotion motor program.

Recent developments in VSD imaging of small neuronal networks.

Voltage-sensitive dye (VSD) imaging is a powerful technique that can provide, in single experiments, a large-scale view of network activity unobtainable with traditional sharp electrode recording methods. Here we review recent work using VSDs to study small networks and highlight several results from this approach. Topics covered include circuit mapping, network multifunctionality, the network basis of decision making, and the presence of variably participating neurons in networks.

Axonal conduction block as a novel mechanism of prepulse inhibition.

In prepulse inhibition (PPI), the startle response to a strong, unexpected stimulus is diminished if shortly preceded by the onset of a different stimulus. Because deficits in this inhibitory gating process are a hallmark feature of schizophrenia and certain other psychiatric disorders, the mechanisms underlying PPI are of significant interest. We previously used the invertebrate model system Tritonia diomedea to identify the first cellular mechanism for PPI--presynaptic inhibition of transmitter release from the afferent neurons (S-cells) mediating the startle response.

Variable neuronal participation in stereotypic motor programs.

To what extent are motor networks underlying rhythmic behaviors rigidly hard-wired versus fluid and dynamic entities? Do the members of motor networks change from moment-to-moment or from motor program episode-to-episode? These are questions that can only be addressed in systems where it is possible to monitor the spiking activity of networks of neurons during the production of motor programs. We used large-scale voltage-sensitive dye (VSD) imaging followed by Independent Component Analysis spike-sorting to examine the extent to which the neuronal network underlying the escape swim behavior of Tritonia diomedea is hard-wired versus fluid from a moment-to-moment perspective. We found that while most neurons were dedicated to the swim network, a small but significant proportion of neurons participated in a surprisingly variable manner.

Validation of independent component analysis for rapid spike sorting of optical recording data.

Independent component analysis (ICA) is a technique that can be used to extract the source signals from sets of signal mixtures where the sources themselves are unknown. The analysis of optical recordings of invertebrate neuronal networks with fast voltage-sensitive dyes could benefit greatly from ICA. These experiments can generate hundreds of voltage traces containing both redundant and mixed recordings of action potentials originating from unknown numbers of neurons.

Parameter space analysis suggests multi-site plasticity contributes to motor pattern initiation in Tritonia.

This research examines the mechanisms that initiate rhythmic activity in the episodic central pattern generator (CPG) underlying escape swimming in the gastropod mollusk Tritonia diomedea. Activation of the network is triggered by extrinsic excitatory input but also accompanied by intrinsic neuromodulation and the recruitment of additional excitation into the circuit. To examine how these factors influence circuit activation, a detailed simulation of the unmodulated CPG network was constructed from an extensive set of physiological measurements.

A stereo-compound hybrid microscope for combined intracellular and optical recording of invertebrate neural network activity.

Optical recording studies of invertebrate neural networks with voltage-sensitive dyes seldom employ conventional intracellular electrodes. This may in part be due to the traditional reliance on compound microscopes for such work. While such microscopes have high light-gathering power, they do not provide depth of field, making working with sharp electrodes difficult.

Long-term habituation in the marine mollusc Tritonia diomedea.

Tritonia diomedea is one of several gastropod molluscs used to study cellular mechanisms of learning and memory. Previous studies in this organism have focused on short-term habituation and sensitization. This report presents the first detailed description of long-term habituation in Tritonia.

A cellular mechanism for prepulse inhibition.

In prepulse inhibition (PPI), startle responses to sudden, unexpected stimuli are markedly attenuated if immediately preceded by a weak stimulus of almost any modality. This experimental paradigm exposes a potent inhibitory process, present in nervous systems from invertebrates to humans, that is widely considered to play an important role in reducing distraction during the processing of sensory input. The neural mechanisms mediating PPI are of considerable interest given evidence linking PPI deficits with some of the cognitive disorders of schizophrenia.

Highly dissimilar behaviors mediated by a multifunctional network in the marine mollusk Tritonia diomedea.

Several motor networks have now been found to be multifunctional, in which one group of neurons participates in the generation of multiple behavioral motor programs. Not surprisingly, the behaviors involved are frequently closely related, often using the same or similar muscle groups. Here we describe an interneuronal network in the marine mollusk Tritonia diomedea that is involved in producing two highly dissimilar behaviors, rhythmic, muscle-based escape swimming and nonrhythmic, cilia-mediated crawling.