Although behavior is ultimately guided by decision-making neurons and their associated networks, the mechanisms underlying neural decision-making in a behaviorally relevant context remain mostly elusive. To address this question, we analyzed goldfish escapes in response to distinct visual looming stimuli with high-speed video and compared them with electrophysiological responses of the Mauthner cell (M-cell), the threshold detector that initiates such behaviors. These looming stimuli evoke powerful and fast body-bend (C-start) escapes with response probabilities between 0.7 and 0.91 and mean latencies ranging from 142 to 716 ms. Chronic recordings showed that these C-starts are correlated with M-cell activity. Analysis of response latency as a function of the different optical parameters characterizing the stimuli suggests response threshold is closely correlated to a dynamically scaled function of angular retinal image size, (t), specifically (t) ϭ (t Ϫ ␦ ϫ e Ϫ ␤ (t Ϫ ␦) , where the exponential term progressively reduces the weight of (t). Intracellular recordings show that looming stimuli typically evoked bursts of graded EPSPs with peak amplitudes up to 9 mV in the M-cell. The proposed scaling function (t) predicts the slope of the depolarizing envelope of these EPSPs and the timing of the largest peak. An analysis of the firing rate of presynaptic inhibitory interneurons suggests the timing of the EPSP peak is shaped by an interaction of excitatory and inhibitory inputs to the M-cell and corresponds to the temporal window in which the probabilistic decision of whether or not to escape is reached.

Activation of auditory afferents on the lateral dendrite of the Mauthner (M)-cell triggers an escape response (C-start) in goldfish. To study distinct behavioral changes and their physiological correlates on a cellular level we examined the effect of acute changes of temperature on M-cell membrane properties and intracellular responses to sound clicks and on C-start kinematics and behavior, focusing on threshold and initial escape direction, two properties determined on the M-cell level. Cooling slowed C-start motor performance, increasing response latency and decreasing peak velocity and peak acceleration, but increased the probability of triggering the escape. In addition, the likelihood of escapes in an inappropriate direction (e.g., responses toward the stimulus instead of away from it) increased at low temperatures. On a cellular level, cooling caused a distinct increase in input resistance of the M-cell and in the dendritic space constant for the auditory-evoked synaptic potentials. Moreover, cooling decreased the magnitude and delayed the onset of feedforward inhibition of the M-cell. These temperature-induced changes in the network and in the intrinsic M-cell properties combine to support behavioral hyperexcitability, but apparently also alter the directional decision-making process during an escape. More generally, our results illustrate that the balance between excitatory and inhibitory influences can determine the expression of a behavior and its modification and at the same time underline the significance of temperature for nervous system function and behavior.

SUMMARY Startle behaviors in teleost fishes are well suited for investigations of mechanisms of sensorimotor integration because the behavior is quantifiable and much of the underlying circuitry has been identified. The teleost C-start is triggered by an action potential in one of the two Mauthner (M) cells. To correlate C-start behavior with electrophysiology, extracellular recordings were obtained from the surface of the medulla oblongata in the hindbrain,close to the M-axons, in freely swimming goldfish monitored using high-speed video. The recordings included action potentials generated by the two M-axons,as well as neighboring axons in the dorsal medial longitudinal fasciculus. Axonal backfills indicated that the latter originate from identifiable reticulospinal somata in rhombomeres 2-8 and local interneurons. Diverse auditory and visual stimuli evoked behaviors with kinematics characteristic of the C-start, and the amplitude of the first component of the hindbrain field potential correlated with the C-start direction. The onset of the field potential preceded that of the simultaneously recorded trunk EMG and movement initiation by 1.08±0.04 and 8.13±0.17 ms, respectively. A subsequent longer latency field potential was predictive of a counterturn. These results indicate that characteristic features of the C-start can be extracted from the neural activity of the M-cell and a population of other reticulospinal neurons in free-swimming goldfish.

To determine the sensory information encoded and the relative contributions of these two transmission modes, M-cell responses to acoustic stimuli in air were recorded intracellularly. Excitatory postsynaptic potentials (EPSPs) evoked by both short 100-to 900-Hz "pips" and longer-lasting amplitude-and frequency-modulated sounds were dominated by fast, repetitive EPSPs superimposed on an underlying slow depolarization. Fast EPSPs 1) have kinetics comparable to presynaptic action potentials, 2) are maximal on the distal lateral dendrite, and 3) are insensitive to GluR antagonists. They presumably are coupling potentials, and power spectral analysis indicated they constitute a high-pass signal that accurately tracks sound frequency and amplitude. The spatial profile of the slow EPSP suggests both proximal and distal dendritic sources, a result supported by predictions of a multicompartmental model and the effects of AMPAR antagonists, which preferentially reduced the proximal component. Thus a second class of afferents generates a portion of the slow EPSP that, with sound stimuli, demonstrate that the dominant mode of transmission at LMCE synapses is electrical. The slow EPSP is a dynamic, low-pass representation of stimulus strength. Accordingly, amplitude and phase information, which are segregated in other systems, are faithfully represented in the M-cell.

Prepulse inhibition (PPI) is typically associated with an attenuation of auditory startle behavior in mammals and is presumably mediated within the brainstem startle circuit. However, the inhibitory mechanisms underlying PPI are not yet clear. We addressed this question with complementary behavioral and in vivo electrophysiological experiments in the startle escape circuit of goldfish, the Mauthner cell (M-cell) system. In the behavioral experiments we observed a 77.5% attenuation (PPI) of startle escape probability following auditory prepulse-pulse stimulation. The PPI effect was observed for prepulse-pulse interstimulus intervals (ISIs) ranging from 20 to 600 ms and its magnitude depended linearly on prepulse intensity over a range of 14 dB. Electrophysiological recordings of synaptic responses to a sound pulse in the M-cell, which is the sensorimotor neuron initiating startle escapes, showed a 21% reduction in amplitude of the dendritic postsynaptic potential (PSP) and a 23% reduction of the somatic PSP following a prepulse. In addition, a prepulse evoked a long-lasting (500 ms) decrease in M-cell excitability indicated by 1) an increased threshold current, 2) an inhibitory shunt of the action potential (AP), and 3) by a linearized M-cell membrane, which effectively impedes M-cell AP generation. Comparing the magnitude and kinetics of inhibitory shunts evoked by a prepulse in the M-cell dendrite and soma revealed a disproportionately larger and longer-lasting inhibition in the dendrite. These results suggest that the observed PPI-type attenuation of startle behavior can be correlated to distinct postsynaptic mechanisms mediated primarily at the M-cell lateral dendrite.