Removing a single neuron in a vertebrate brain forever abolishes an essential behavior

Abstract

The giant Mauthner (M) cell is the largest neuron known in the vertebrate brain. It has enabled major breakthroughs in neuroscience but its ultimate function remains surprisingly unclear: An actual survival value of M cell-mediated escapes has never been supported experimentally and ablating the cell repeatedly failed to eliminate all rapid escapes, suggesting that escapes can equally well be driven by smaller neurons. Here we applied techniques to simultaneously measure escape performance and the state of the giant M axon over an extended period following ablation of its soma. We discovered that the axon survives remarkably long and remains still fully capable of driving rapid escape behavior. By unilaterally removing one of the two M axons and comparing escapes in the same individual that could or could not recruit an M axon, we show that the giant M axon is essential for rapid escapes and that its loss means that rapid escapes are also lost forever. This allowed us to directly test the survival value of the M cell-mediated escapes and to show that the absence of this giant neuron directly affects survival in encounters with a natural predator. These findings not only offer a surprising solution to an old puzzle but demonstrate that even complex brains can trust vital functions to individual neurons. Our findings suggest that mechanisms must have evolved in parallel with the unique significance of these neurons to keep their axons alive and connected.

Intersection of motor volumes predicts the outcome of ambush predation of larval zebrafish

“…Since this range composes a significant proportion of the experimentally observed range of times remaining at escape, there is a clear functional benefit of recruiting the Mauthner neuron in this predatory context. This is further supported by recent experimental evidence which shows that larval zebrafish are far less likely to survive dragonfly nymph strikes after Mauthner cell ablation [16].…”

“…Fish motor volumes representing Mauthner active and silent responses ( Figure 7D) were generated by pseudo-randomly sampling different uniform distributions of initial bend velocities. The range of bend velocities for Mauthner silent motor volumes was 10 ± 5 deg/sec and for Mauthner active motor volumes it was 18 ± 5 deg/sec based on prior studies that investigated bend velocities of free swimming larval zebrafish before and after Mauthner ablation [41,42,16]. The ranges were also constructed to have some overlap since studies have found that Mauthner active and silent responses can on occasion produce similar kinematics [43,44].…”

“…Moreover, in many animals, escapes can be initiated with or without the activation of large diameter command neurons devoted to generating the shortest latency escapes with the fastest speeds [12,13,14]. Specifically, larval zebrafish (Danio rerio), a popular model system for linking neural circuits to escape behaviors [15], are dramatically less likely to survive an attack from a predator after photo-ablation of the command-like neurons devoted to generating escape responses in fish called Mauthner cells [16]. However, other results have both disputed and supported the utility of fast speeds for increasing evasion success [17,18,19,20,21,22,23,24,25].…”

The formin Fmn2 is required for the development of an excitatory interneuron module in the zebrafish acoustic startle circuit

“…Zebrafish is an excellent vertebrate model to interrogate gene function in the establishment of neural circuits in vivo and associated behaviours (Kalueff et al, 2013;Mcarthur et al, 2020). One of the most studied neural circuits is the Mauthner cell mediated acoustic startle circuit (Swain et al, 1993;Jontes et al, 2000;Korn and Faber, 2005;Burgess et al, 2009;Sillar, 2009;Issa et al, 2011;Kinkhabwala et al, 2011;Hale et al, 2016;Liu and Hale, 2017;Hecker et al, 2020). Acoustic and tactile stimuli from the environment are processed by the M-cells aided by regulatory excitatory and inhibitory interneuron module and relayed to the motor neurons downstream (Korn and Faber, 2005).…”

Brain cell somatic gene recombination and its phylogenetic foundations

“…Issues range from access to consistent, high-quality human autopsy materials of comparable age, sex, and race or sequencing technologies and bioinformatics not optimized for mosaicism to biological impediments like nonclonal genomic alterations affecting just a single postmitotic cell, obfuscated by a sea of normal cells. For example, the brain shows functional uniqueness of very small populations of cells, such as neurons responsive to input from a particular point in visual space (30,31) or even the proposed single "grandmother" cell that responds to a complex assembly of visual features such as those comprising a specific face (32), yet most sequencing techniques only allow detection of de novo somatic mutations present in .1-10% of cells (33). In the human brain, this represents a background of tens of billions (10 10 ) of unaffected cells preventing mutation detection even for some clonally expanded mutations, let alone isolated single-cell changes that would require sequencing sensitivity and specificity many logs beyond current technologies.…”