Free-energy and the brain

If one formulates Helmholtz's ideas about perception in terms of modern-day theories one arrives at a model of perceptual inference and learning that can explain a remarkable range of neurobiological facts. Using constructs from statistical physics it can be shown that the problems of inferring what cause our sensory input and learning causal regularities in the sensorium can be resolved using exactly the same principles. Furthermore, inference and learning can proceed in a biologically plausible fashion. The ensuing scheme rests on Empirical Bayes and hierarchical models of how sensory information is generated. The use of hierarchical models enables the brain to construct prior expectations in a dynamic and context-sensitive fashion. This scheme provides a principled way to understand many aspects of the brain's organisation and responses.In this paper, we suggest that these perceptual processes are just one emergent property of systems that conform to a free-energy principle. The free-energy considered here represents a bound on the surprise inherent in any exchange with the environment, under expectations encoded by its state or configuration. A system can minimise free-energy by changing its configuration to change the way it samples the environment, or to change its expectations. These changes correspond to action and perception respectively and lead to an adaptive exchange with the environment that is characteristic of biological systems. This treatment implies that the system's state and structure encode an implicit and probabilistic model of the environment. We will look at models entailed by the brain and how minimisation of free-energy can explain its dynamics and structure

The mechanism of action of capsaicin on sensory C-type neurones and their axons in vitro

The mechanism of action of the sensory neurotoxin, capsaicin, on visceral afferent fibres and ganglion cells has been studied using electrophysiological and histological techniques. Extracellular in vitro recording from adult vagus nerves revealed a depolarization and a reduced C-spike amplitude. These probably reflect effects on unmyelinated sensory fibres, since no such action was detected in fibre trunks lacking sensory fibres, such as preganglionic sympathetic nerves and ventral spinal roots. Ion substitution experiments indicated that the capsaicin-induced depolarization is mediated by a mechanism that involves sodium (Na+) calcium (Ca2+) and, to a lesser extent chloride, (Cl-) ions. In vitro intracellular recordings from sensory neurone perikarya, showed that capsaicin depolarizes 70% of the C-type neurones located within the rat nodose ganglion. The capsaicin-induced depolarization was primarily mediated by an increase by an in membrane conductance to Na+ and Ca2+. An additional membrane conductance increase to potassium (K+) was also induced. However, this depended on an influx of calcium via the primary conductance mechanism. Histological experiments using light and electron-microscopic techniques indicated that capsaicin can induce substantial cytotoxic damage to a subpopulation of nodose sensory neurones and vagus nerve unmyelinated fibres. Moreover, the cytotoxic effects could be induced by short applications (< 10 mins) and low concentrations (1-10 μM) of capsaicin. The entry of calcium ions into the cells appeared to play a major role in the cytotoxic process, as the replacement of extracellular calcium with magnesium minimised the cytotoxic damage. The failure of calcium channel-blockers to reduce the calcium-dependent neurotoxic effect indicated that calcium entry through capsaicin-activated channels, rather than voltage-gated calcium channels, initiates the cytotoxicity. It is suggested that capsaicin opens cationic channels and that calcium entry through these channels might not only modify cell excitability but also prime the neurotoxic process which can lead to cell death