PubMed Health⌕ Search

Biomedical subjects

Donald S Faber

Publications and source records attributed to Donald S Faber.

8 recordsLinked to original sources
PubMed2006

Neural representation of object approach in a decision-making motor circuit.

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 kappa(t) = (t-delta x e(-beta(t-delta)), 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 kappa(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.

Animals↗
PubMed2006

Correlation of C-start behaviors with neural activity recorded from the hindbrain in free-swimming goldfish (Carassius auratus).

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.

Animals↗
PubMed2005

The Mauthner cell half a century later: a neurobiological model for decision-making?

The Mauthner (M) cell is a critical element in a vital escape "reflex" triggered by abrupt or threatening events. Its properties at the molecular and synaptic levels, their various forms of plasticity, and the design of its networks, are all well adapted for this survival function. They guarantee that this behavior is appropriately unilateral, variable, and unpredictable. The M cell sets the behavioral threshold, and, acting in concert with other elements of the brainstem escape network, determines when, where, and how the escape is executed.

Animals↗
PubMed2004

Transient electrical coupling delays the onset of chemical neurotransmission at developing synapses.

The formation and subsequent elimination of electrical coupling between neurons has been demonstrated in many developing vertebrate and invertebrate nervous systems. The relationship between the disappearance of electrical synaptic connectivity and the appearance of chemical neurotransmission is not well understood. We report here that identified motoneurons from the snail Helisoma formed transient electrical and chemical connections during regeneration both in vivo and in vitro. Electrical connections that formed in vivo were strongest by day 2 and no longer detectable by day 7. During elimination of this electrical connection, an inhibitory chemical connection from 110 onto 19 formed. This sequence of synaptic development was recapitulated in cell culture with a similar time course. The relationship between the appearance of transient electrical coupling and its possible effects on the subsequent chemical synaptogenesis were examined by reducing transient intercellular coupling. Trophic factor-deprived medium resulted in a 66% reduction in coupling coefficient. In these conditions, the unidirectional chemical connection formed readily; in contrast, chemical synaptogenesis was delayed in cell pairs exposed to trophic factors where transient electrical coupling was strong. Dye coupling and synaptic vesicle cycling studies supported electrophysiological results. Exposure to cholinergic antagonists, curare and hexamethonium bromide, which block chemical neurotransmission in these synapses, resulted in prolonged maintenance of the electrical connection. These studies demonstrated an inverse relationship between chemical and electrical connectivity at early stages of synaptic development and suggest a dynamic interaction between these forms of neuronal communication as adult neural networks are constructed or regenerated.

Animals↗
PubMed2003

Central cellular mechanisms underlying temperature-dependent changes in the goldfish startle-escape behavior.

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.

Acoustic Stimulation↗
PubMed2003

Neurosteroid effects on GABAergic synaptic plasticity in hippocampus.

We have previously reported that short-term (48-72 h) exposure to the GABA-modulatory steroid 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP) increases expression of the alpha4 subunit of the GABA(A) receptor (GABAR) in the hippocampus of adult rats. This change in subunit composition was accompanied by altered pharmacology and an increase in general excitability associated with acceleration of the decay time constant (tau) for GABA-gated current of pyramidal cells acutely isolated from CA1 hippocampus similar to what we have reported following withdrawal from the steroid after chronic long-term administration. Because GABAR can be localized to either synaptic or extrasynaptic sites, we tested the hypothesis that this change in receptor kinetics is mediated by synaptic GABAR. To this end, we evaluated the decay kinetics of TTX-resistant miniature inhibitory postsynaptic currents (mIPSCs) recorded from CA1 pyramidal cells in hippocampal slices following 48-h treatment with 3alpha,5alpha/beta-THP (10 mg/kg, ip). Hormone treatment produced a marked acceleration in the fast decay time constant (tau(fast)) of GABAergic mIPSCs. This effect was prevented by suppression of alpha4-subunit expression with antisense (AS) oligonucleotide, suggesting that hormone treatment increases alpha4-containing GABAR subsynaptically. This conclusion was further supported by pharmacological data from 3alpha,5beta-THP-treated animals, demonstrating a bimodal distribution of taus for individual mIPSCs following bath application of the alpha4-selective benzodiazepine RO15-4513, with a shift to slower values. Because 40-50% of the individual taus were also shifted to slower values following bath application of the non-alpha4-selective benzodiazepine agonist lorazepam (LZM), we suggest that the number of GABAR synapses containing alpha4 subunits is equivalent to those that do not following 48-h administration of 3alpha,5beta-THP. The decrease in GABAR-mediated charge transfer resulting from accelerated current decay may then result in increased excitability of the hippocampal circuitry, an effect consistent with the increased behavioral excitability we have previously demonstrated.

Affinity Labels↗
PubMed2002

Modulation of synaptic delay during synaptic plasticity.

At most synapses, information about the processes underlying transmitter release evoked by a presynaptic action potential has been gathered indirectly, based on characterization of the postsynaptic response. Traditionally, the two electrophysiological parameters used for this indirect investigation are the amplitude and latency of the response. The amplitude measures amount of transmitter released; the latency (synaptic delay) reflects the kinetics of a sequence of events that culminates in release. The latency distribution of quantal events, or the time course of composite evoked responses, can be used to infer the time course of the elevated release probability following a stimulus. Recent studies have demonstrated that synaptic delay is not invariant, but is modifiable during several forms of short-term synaptic plasticity. This suggests that the step of transmitter secretion can be modulated directly. Several models for short-term synaptic plasticity are evaluated in the context of the observed changes in synaptic delay.

Action Potentials↗