Degenerate Neuronal and Circuit Mechanisms Important for Generating Rhythmic Motor Patterns
authors: Ronald L Calabrese, Eve Marder
doi: 10.1152/physrev.00003.2024
CITATION
Calabrese, R. L., & Marder, E. (2024). Degenerate Neuronal and Circuit Mechanisms Important for Generating Rhythmic Motor Patterns. Physiological Reviews, physrev.00003.2024. https://doi.org/10.1152/physrev.00003.2024
ABSTRACT
In 1996 we published a review article (182) describing the state of knowledge about the structure and function of the central pattern generating circuits important for producing rhythmic behaviors. Although many of the core questions persist, much has changed since 1996. Here, we focus on newer studies that reveal ambiguities that complicate understanding circuit dynamics, despite the enormous technical advances of the recent past. In particular, we highlight recent studies of animal-to-animal variability, our understanding that circuit rhythmicity may be supported by multiple state-dependent mechanisms within the same animal, and that robustness and resilience in the face of perturbation may depend critically on the presence of modulators and degenerate circuit mechanisms. Additionally, we highlight the use of computational models to ask whether there are generalizable principles about circuit motifs that can be found across rhythmic motor systems in different animal species.
fleeting notes
CPGs = central pattern generators
- networks that generate rhythmic movements
- the best understood CPGs are ones with a small number of neurons, large diameter soma
quantitative models can serve 2 purposes:
- validation of insights from experimental work
- building models to ask how a nervous system can achieve something to motivate experiments
parallel CPG pathways enhance resilience of a system
degenerate mechanisms = multiple sets of parameters that can give rise to similar circuit dynamics
- exist for single neurons and circuit functions
- degenerate mechanisms enhance resilience and robustness of a system
postinhibitory rebound
- a hallmark of CPG neurons is producing bursts of spikes after inhibition
- an increase in excitation current that follows synaptic inhibition
- one mechanism is removing sodium or calcium channel inactivation during hyperpolarization - then driving depolarization above threshold
half center oscillators
- reciprocal inhibition can generate rhythms by forming half center oscillators
- escape and release mechanism enables the alternating bursting of each half center
- escape = an inhibited member starts to depolarize through an intrinsic mechanism. it then inhibits the antagonist partner and stops the bursting of the other cell.
- release = bursting member of the half center stops firing because of some intrinsic mechanism and stops inhibiting partner which can then rebound and start bursting
bursting neurons
- neurons that have instrinsically bursting properties.
- the specific set of membrane currents that contribute to bursting vary depending on neuromodulation and physiological contexts
electrical coupling
- found in all nervous systems
- to identify, can use electrical recordings using electrodes in pre and post synaptic cells, dy coupling,
- too small to see in many new connectomes
nonrectifying - current passes equally in both directions
rectifying - current passes in one direction
gap junctions between cells of different types are rectifying
gap junctions between cells of the same type are more likely to be nonrectifying
all circuit diagrams and connectomes have instances of parallel pathways - highlighting degenerate mechanisms
graded transmission
- nonspiking interneurons have graded release of trasnmitter
short term synaptic plasticity
- facilitation, depression
- short term facilitation happens during calcium accumulation in presynaptic terminals
- short term depression results from the depletion of synaptic vesicles
- different terminals of the same neruon can show entirely different paterns of facilitation and depression
neuromodulation
- circulating hormones and peptides and small molecule cotransmitters
- most synapses and ion channels are subject to neuromodulation
- elicit changes over long timescales
- modulatory substances can stabilize and promote robust circuit behavioral functions
using 2 of the best invertebrate circuits to demonstrate principles of understanding circuit dynamics
- leech heartbeat system & crustacean stomatogastric nervous system
leech
- segmentally distributed and regular switching of coordination of motor neurons
- motor nueron firing pattern is imposed by a CPG
- have two hearts that run the length of the leach.
- motor neurons provide excitatory junctional potentials that sum
- constrictions timed by motor neuron bursts - maximal tension is achieved after middle spike of burst
- switches in coordination happen in one beat cycle, always reciprocal
- HN interneurons from the core heartbeat CPG
- motor neurons are rhythmically inhibited by the premotor neurons
STG
- STG innervates teh centralized foregut and maintains a strict firing order among motor neurons
- the motor neurons crucially participate in a CPG
- the pyloric rhythm
- triphasic motor pattern
- PD → LP → PY motor neurons firing order
- AB and two PD neurons are strongly electrically coupled
- AB is an endogenous oscillator and drive PD neurons to burst in synchrony
- 2 major approaches to studying how phase is regulated in pyloric rhythm
- showing a given current or modulator alters the phase of follower neurons
- attempting to account for the multiple mechanisms that might contribute to maintaining the phase when something changes
- the gastric mill rhythm
- episodic and active only when sensory inputs activate the descending modulatory neurons
breathing
-
diaphragm is contracted to fil the lungs
-
then postinspiration - adductor muscles narrow airway
-
expiration is only an active process when enhanced breathing is needed (like exercise) but passive at other times.
-
preBotzinger complex drives inspiration
-
ventral respiratory column runs rostral caudal
-
the triple oscillator model for control of breathing
- oscillation is thought to arise thorugh interaction of excitatory and inhibitory inputs
- rhythmogenesis of the preBotC is produced through cellular mechanisms and excitability of the cells
- inhibition is also very important!
swimming
-
produced by side to side alteration of axial muscle contractions in each body segment along a wave
-
fish have slow, intermediate and fast muscle fibers that are recruited sequentially as speed increases
-
larval zebrafish are actively developing and have changing neural circuitry
-
inhibitions is really important
-
can make a prep to expose spinal cord and brain stem but leave tail muscles intact. so can patch clamp neurons, stimulate, and image neurons, while also recording motor neurons
- this can be a prep to study fictive swimming
-
4 motor pools
- primary motor neurons are fast, involved in escape
- secondary are fast, intermediate and slow
-
V2a interneurons are diverse
- active during fictive swimming
- organized into 3 functional modules
- show bursting pacemaker properties
-
nMLF are descending excitatory neurons
- increase activity with increased speed
- stop activity with cessation of swimming
highlights
“Therefore, it is not an accident that the central pattern generators that are best understood include those with a small number of neurons, all or most of which have large diameter somata, such as in the leech heartbeat system (7), the crustacean stomatogastric nervous system (5), and the Tritona (3, 8) swim system, to name only a few.”Page 2
“Electrical coupling can be nonrectifying, in which current passes equally well in both directions, or rectifying, in which current passes preferentially in one direction, although the degree of rectification varies a good deal. In general, it is thought that junctions between cells of different types are often rectifying”Page 6
“Junctions between neurons of the same cell type (73) are more likely to be nonrectifying”Page 6
“Nonetheless, because the existence of gap junctions in most circuits is almost certainly underestimated, it is difficult to ascertain how much this lack of knowledge is compromising our understanding of circuit dynamics”Page 8
“This study also shows that there are three distinct circuit mechanisms that can produce similar changes in circuit output, again illustrating the importance of degeneracy in neuronal dynamics”Page 9
“Since the discovery of local nonspiking interneurons and their graded release of transmitter onto postsynaptic targets in arthropod locomotor circuits (77, 78), graded release of transmitter has been recognized as important in several invertebrate motor networks”Page 9