Speed-dependent cellular decision making in nonequilibrium genetic circuits

Despite being governed by the principles of nonequilibrium transitions, gene expression dynamics underlying cell fate decision is poorly understood. In particular, the effect of signaling speed on cellular decision making is still unclear. Here we show that the decision between alternative cell fates, in a structurally symmetric circuit, can be biased depending on the speed at which the system is forced to go through the decision point. The circuit consists of two mutually inhibiting and self-activating genes, forced by two external signals with identical stationary values but different transient times. Under these conditions, slow passage through the decision point leads to a consistently biased decision due to the transient signaling asymmetry, whereas fast passage reduces and eventually eliminates the switch imbalance. The effect is robust to noise and shows that dynamic bifurcations, well known in nonequilibrium physics, are important for the control of genetic circuits.     

Wiring optimization in cortical circuits

Wiring a brain presents a formidable problem because neural circuits require an enormous number of fast and durable connections. We propose that evolution was likely to have optimized neural circuits to minimize conduction delays in axons, passive cable attenuation in dendrites, and the length of "wire" used to construct circuits, and to have maximized the density of synapses. Here we ask the question: "What fraction of the volume should be taken up by axons and dendrites (i.e., wire) when these variables are at their optimal values?" The biophysical properties of axons and dendrites dictate that wire should occupy 3/5 of the volume in an optimally wired gray matter. We have measured the fraction of the volume occupied by each cellular component and find that the volume of wire is close to the predicted optimal value.     

Decision making in recurrent neuronal circuits

Decision making has recently emerged as a central theme in neurophysiological studies of cognition, and experimental and computational work has led to the proposal of a cortical circuit mechanism of elemental decision computations. This mechanism depends on slow recurrent synaptic excitation balanced by fast feedback inhibition, which not only instantiates attractor states for forming categorical choices but also long transients for gradually accumulating evidence in favor of or against alternative options. Such a circuit endowed with reward-dependent synaptic plasticity is able to produce adaptive choice behavior. While decision threshold is a core concept for reaction time tasks, it can be dissociated from a general decision rule. Moreover, perceptual decisions and value-based economic choices are described within a unified framework in which probabilistic choices result from irregular neuronal activity as well as iterative interactions of a decision maker with an uncertain environment or other unpredictable decision makers in a social group.     

Training in ethical decision making

Advances in biotechnology and evolving attitudes of biomedical professionals and members of the general public toward illness, medical care, and research generate topics for ethics discussions. The author offers advice for training animal care staff in ethical decision making.     

Consensus decision making in animals

Individual animals routinely face decisions that are crucial to their fitness. In social species, however, many of these decisions need to be made jointly with other group members because the group will split apart unless a consensus is reached. Here, we review empirical and theoretical studies of consensus decision making, and place them in a coherent framework. In particular, we classify consensus decisions according to the degree to which they involve conflict of interest between group members, and whether they involve either local or global communication; we ask, for different categories of consensus decision, who makes the decision, what are the underlying mechanisms, and what are the functional consequences. We conclude that consensus decision making is common in non-human animals, and that cooperation between group members in the decision-making process is likely to be the norm, even when the decision involves significant conflict of interest.     

Facts and reflections on thalamo cortical reverberation of impulses

Experiments on cats, either unanesthetized or anesthetized with various doses of pentobarbital, showed that the cortical rhythmic after-discharge ("slow after-activity"), which has been regarded as a manifestation of reverberation of impulses in thalamocortical circuits [17], consists of a burst of spontaneous "spindles" evoked by stimulation. This conclusion is supported by the following facts: Spontaneous "spindles" and the rhythmic after-discharge respond absolutely identically (disappear) to activation of the EEG and deepening of pentobarbital anesthesia. The absence of thalamocortical reverberation is also indicated by the preservation of a rhythmic after-discharge (to clicks), synchronous with the cortex, in the thalamic relay nucleus (the medial geniculate body) after cooling or after removal of its projection zone.     

Ethical decision making by Canadian family physicians.

Canadian family physicians were sent questionnaires that asked how they would handle the ethical problems posed by six sample cases and what reasons were relevant to their decisions. The ethical problems concerned how much information to divulge to patients, how extensively a physician should become involved in the lifestyles of patients and how to deal with a possible family problem. The study identified characteristics of family physicians that affect their ethical decision making and tested a theoretical model that regards ethical problems as conflicts between respecting patient autonomy and promoting patient welfare. The varied responses suggested that ethical issues are resolved on a case-by-case, rather than a theoretical, basis. Certification in family medicine was the only characteristic associated with a consistent pattern of responses; certificants were more likely than other physicians to involve patients in decisions.     

Critical period plasticity in local cortical circuits

Neuronal circuits in the brain are shaped by experience during 'critical periods' in early postnatal life. In the primary visual cortex, this activity-dependent development is triggered by the functional maturation of local inhibitory connections and driven by a specific, late-developing subset of interneurons. Ultimately, the structural consolidation of competing sensory inputs is mediated by a proteolytic reorganization of the extracellular matrix that occurs only during the critical period. The reactivation of this process, and subsequent recovery of function in conditions such as amblyopia, can now be studied with realistic circuit models that might generalize across systems.     

Temporal decision making in complex environments

The basic hypothesis of the author is that under the influence of technological development and market pressure, situations take on temporal characteristics that are more and more difficult for the operator to control. The temporal strategies traditionally installed by the operator disappear, are transferred or transformed. Far from counterbalancing these phenomena, the displays, as they are designed in the workplace, obliterate the temporal dimension. The errors that are seen to appear are the product of a mismatch between the characteristics of the situation and the operator's resources. Four mechanisms of time estimation are discussed. Field study results on temporal strategies, such as anticipation, assessment of a process evolution and planning adjustment are developed.     

Regulation of spike timing in visual cortical circuits

A train of action potentials (a spike train) can carry information in both the average firing rate and the pattern of spikes in the train. But can such a spike-pattern code be supported by cortical circuits? Neurons in vitro produce a spike pattern in response to the injection of a fluctuating current. However, cortical neurons in vivo are modulated by local oscillatory neuronal activity and by top-down inputs. In a cortical circuit, precise spike patterns thus reflect the interaction between internally generated activity and sensory information encoded by input spike trains. We review the evidence for precise and reliable spike timing in the cortex and discuss its computational role.