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Biology subjects

Ehrlich, D. E.

Publications and source records attributed to Ehrlich, D. E..

7 recordsLinked to original sources

Critical period plasticity enables credit assignment

Synaptic plasticity is often guided by instructive inputs to neural circuits, but learning only succeeds when these instructions reach neurons that mediate relevant outputs. This creates the credit assignment problem: how does a neuron receive instructions suited to its own behavioral function? Here we report a developmental mechanism that enables credit assignment by using instructive inputs to organize the downstream architecture through which learning is expressed. In the olivocerebellar learning system, the inferior olive provides instructive inputs that guide plasticity within the cerebellum. During circuit assembly in zebrafish, we find these same inputs regulate long-range cerebellar projections during a highly plastic, two-day critical period. Developmental experience caused specific maturation of projections to targets that were coactivated with olivary inputs. Mathematical theory and computational modeling show how the resulting architecture constrains later learning, such that a single input can sculpt downstream connectivity and then leverage that circuit to assign credit. Simulated learning became paradoxically more robust if we reduced plasticity after a developmental critical period, protecting key architecture from corruption during learning. Thus, instructive inputs can first build the circuits they later teach, coordinating development and learning to enable effective credit assignment.

neuroscience↗

Direct cerebellar control over motor production in a species with extreme cerebellar enlargement

The cerebellum is thought to fine-tune movement without being required for its production. However, this textbook view derives mainly from studies of mammalian species with highly developed cerebral cortices. Here we examined cerebellar function in the elephant-nose fish, a member of a family of African weakly electric fish (Mormyridae) in which the cerebellum is massively enlarged. The elephant-nose fish is named for a flexible facial appendage that is used to probe surfaces and extract prey from substrate. Results from microstimulation, electrophysiological recordings, and lesions support a direct role for the C1 region of the mormyrid cerebellum in controlling movement of this appendage. These findings suggest that the cerebellum is capable of performing functions typically ascribed to the cerebral cortex, emphasizing the importance of evolutionary history on the functional specialization of brain regions.

neuroscience↗

A brainstem circuit for gravity-guided vertical navigation

The sensation of gravity anchors our perception of the environment and is crucial for navigation. However, the neural circuits that transform gravity into commands for navigation are undefined. We first determined that larval zebrafish (Danio rerio) navigate vertically by maintaining a consistent heading across a series of upward climb or downward dive bouts. Gravity-blind mutant fish swim with more variable heading and excessive veering, leading to inefficient vertical navigation. After targeted photoablation of ascending vestibular neurons and spinal projecting midbrain neurons, but not vestibulospinal neurons, vertical navigation was impaired. These data define a sensorimotor circuit that uses evolutionarily-conserved brainstem architecture to transform gravitational signals into persistent heading for vertical navigation. The work lays a foundation to understand how vestibular inputs allow animals to move efficiently through their environment.

neuroscience↗

Behavioral control through the direct, focal silencing of neuronal activity

Voltage-gated sodium channel (NaV) activity underlies electrical signaling, synaptic release, circuit function, and, ultimately, behavior. Molecular tools that enable precise control of NaV subpopulations make possible temporal regulation of neuronal activity and cellular communication. To rapidly modulate NaV currents, we have rendered a potent NaV inhibitor, saxitoxin, transiently inert through chemical protection with a novel nitrobenzyl-derived photocleavable group. Light-induced uncaging of the photocaged toxin, STX-bpc, effects rapid inhibitor release and focal NaV block. We demonstrate the efficacy of this reagent for manipulating action potentials in mammalian neurons and brain slice and for altering locomotor behavior in larval zebrafish. Photo-uncaging of STX-bpc is a non-invasive, effective method for reversible, spatiotemporally precise tuning of NaV currents, application of which requires no genetic manipulation of the biological sample.

neuroscience↗

Hatchling fish disperse using an efficient multisensory strategy

Animals improve fitness by choosing when and where to disperse in the environment using sensory cues. In freshwater habitats subject to flood and drought, dispersal can urgently challenge newly hatched fish. Here we manipulated rearing environment and sensory systems to reveal an adaptive sensorimotor strategy for dispersal. If we constrained hatchlings or blocked feedback about motion by simultaneously impairing the lateral line and vision, they gulped air and elevated their buoyancy to passively sail on faster surface waters. In stagnant water, hatchlings then covered more ground with hyperstable swimming, tightly steering based on graviception. In hydrodynamic simulations, these adaptations nearly tripled diffusivity and made dispersal robust to local conditions. Through combined use of three senses, hatchlings adapt their behavior to flexibly and efficiently disperse.

animal behavior and cognition↗

A primal role for balance in the development of coordinated locomotion

Mature locomotion requires that animal nervous systems coordinate distinct groups of muscles. The pressures that guide the development of coordination are not well understood. We studied vertical locomotion in developing zebrafish to understand how and why coordination might emerge. We found that zebrafish used their pectoral fins and bodies synergistically to climb. As they developed, zebrafish came to coordinate their fins and bodies to climb with increasing postural stability. Fin-body synergies were absent in mutants with-out vestibular sensation, linking balance and coordination. Similarly, synergies were systematically altered following cerebellar lesions, identifying a neural substrate regulating fin-body coordination. Computational modeling illustrated how coordinated climbing could improve balance as zebrafish mature. Together these findings link the sense of balance to the maturation of coordinated locomotion. As they develop, zebrafish improve postural stability by optimizing fin-body coordination. We therefore propose that the need to balance drives the development of coordinated locomotion.

neuroscience↗

A novel mechanism for volitional locomotion in larval zebrafish

To locomote stably, animals must coordinate volitional actions that change posture with opposing reflexes that hold posture constant [1-8]. These conflicting actions are thought to necessitate integrated control, in which reflexes are modulated to permit or even produce volitional movements [9-14]. Here we report that larval zebrafish (Danio rerio) utilize a simpler control scheme featuring independent volitional and reflexive movements. We present behavioral evidence that larvae swim in depth by appending destabilizing trunk rotations to steer with independent rotations to balance. When we manipulated buoyancy to deflect fish up or down, they redirected steering without coordinated changes to their balance reflex. As balance developed and increasingly opposed destabilization-mediated steering, larvae acquired compensatory use of their pectoral fins to steer. Removing the pectoral fins from older larvae impaired steering but preserved the strong balance reflex. Consequentially, older larvae without fins were strikingly less maneuverable -- unable to revert to destabilization-mediated steering -- revealing a rigidity inherent within the framework of independent volitional and reflexive control. Larval zebrafish therefore produce effective but inflexible locomotion by sequencing independent volitional and reflexive movements. These results reveal a simple control scheme, applicable for robotic design, that solves the general problem of coordinating volitional movements with the vital reflexes that oppose them.

neuroscience↗