A free-energy principle has been proposed recently that accounts for action, perception and learning. This Review looks at some key brain theories in the biological (for example, neural Darwinism) and physical (for example, information theory and optimal control theory) sciences from the free-energy perspective. Crucially, one key theme runs through each of these theories — optimization. Furthermore, if we look closely at what is optimized, the same quantity keeps emerging, namely value (expected reward, expected utility) or its complement, surprise (prediction error, expected cost). This is the quantity that is optimized under the free-energy principle, which suggests that several global brain theories might be unified within a free-energy framework.

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The free-energy principle: a unified brain theory?

Prelude. Cycle 1. Introduction. Cycle 2. Structure defines function. Cycle 3. Diversity of cortical functions is provided by inhibition. Cycle 4. Windows on the brain. Cycle 5. A system of rhythms: from simple to complex dynamics. Cycle 6. Synchronization by oscillation. Cycle 7. The brain's default state: self-organized oscillations in rest and sleep. Cycle 8. Perturbation of the default patterns by experience. Cycle 9. The gamma buzz: gluing by oscillations in the waking brain. Cycle 10. Perceptions and actions are brain state-dependent. Cycle 11. Oscillations in the "other cortex:" navigation in real and memory space. Cycle 12. Coupling of systems by oscillations. Cycle 13. The tough problem. References.

Rhythms of the brain

The ionotropic glutamate receptors are ligand-gated ion channels that mediate the vast majority of excitatory neurotransmission in the brain. The cloning of cDNAs encoding glutamate receptor subunits, which occurred mainly between 1989 and 1992 ([Hollmann and Heinemann, 1994][1]), stimulated this

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The glutamate receptor ion channels

1980 Preface * 1999 Preface * 1999 Acknowledgements * Introduction * 1 Circular Logic * 2 Phase Singularities (Screwy Results of Circular Logic) * 3 The Rules of the Ring * 4 Ring Populations * 5 Getting Off the Ring * 6 Attracting Cycles and Isochrons * 7 Measuring the Trajectories of a Circadian Clock * 8 Populations of Attractor Cycle Oscillators * 9 Excitable Kinetics and Excitable Media * 10 The Varieties of Phaseless Experience: In Which the Geometrical Orderliness of Rhythmic Organization Breaks Down in Diverse Ways * 11 The Firefly Machine 12 Energy Metabolism in Cells * 13 The Malonic Acid Reagent ('Sodium Geometrate') * 14 Electrical Rhythmicity and Excitability in Cell Membranes * 15 The Aggregation of Slime Mold Amoebae * 16 Numerical Organizing Centers * 17 Electrical Singular Filaments in the Heart Wall * 18 Pattern Formation in the Fungi * 19 Circadian Rhythms in General * 20 The Circadian Clocks of Insect Eclosion * 21 The Flower of Kalanchoe * 22 The Cell Mitotic Cycle * 23 The Female Cycle * References * Index of Names * Index of Subjects

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/596B270197FE27DE5FABB598B6210622/S0025557200150892a.pdf/div-class-title-span-class-italic-the-geometry-of-biological-time-span-by-a-t-winfree-pp-544-dm68-corrected-second-printing-1990-isbn-3-540-52528-9-springer-div.pdf

The geometry of biological time , by A. T. Winfree. Pp 544. DM68. Corrected Second Printing 1990. ISBN 3-540-52528-9 (Springer)

Neuronal activity in the brain gives rise to transmembrane currents that can be measured in the extracellular medium. Although the major contributor of the extracellular signal is the synaptic transmembrane current, other sources — including Na+ and Ca2+ spikes, ionic fluxes through voltage- and ligand-gated channels, and intrinsic membrane oscillations — can substantially shape the extracellular field. High-density recordings of field activity in animals and subdural grid recordings in humans, combined with recently developed data processing tools and computational modelling, can provide insight into the cooperative behaviour of neurons, their average synaptic input and their spiking output, and can increase our understanding of how these processes contribute to the extracellular signal.

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The origin of extracellular fields and currents — EEG, ECoG, LFP and spikes

The hippocampus plays a central role in long-term memory formation, and different hippocampal network states are thought to play distinct roles in this process. These network states are controlled by neuromodulatory inputs, in particular the cholinergic input from the medial septum. Here, we used optogenetic stimulation of septal cholinergic neurons to better understand how cholinergic activity affects different stages of spatial memory formation in a reward-based navigation task in mice. We found that optogenetic stimulation of septal cholinergic neurons (1) impaired memory formation when activated at goal location but not during navigation; (2) reduced sharp wave-ripple incidence at goal location; and (3) reduced ripple incidence and enhanced thetagamma oscillations during sleep. These results underscore the importance of appropriate timing of cholinergic input in long-term memory formation, which might help explain why there has been limited success of cholinesterase inhibitor drugs in the treatment of memory impairment in Alzheimer9s disease.

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Cholinergic suppression of sharp wave-ripples impairs hippocampus-dependent spatial memory

Lateralization of brain function has primarily been studied at the macroscopic level. Studies have detected gross anatomical differences in neuron types, numbers, distribution, and connectivity and related these to functional divisions between the two hemispheres. Comparatively little is known about lateralization of synaptic function. A notable exception to this is the recently uncovered lateralization of receptor composition, structure, and function of hippocampal Cornu Ammonis (CA)3–CA1 synapses in rodents. Electrophysiological and electron microscopic studies have revealed that synapses made by the left CA3 onto CA1 neurons on either side of the hippocampus exhibit distinct receptor composition and morphology from those made by the right CA3. Here, we discuss how optogenetic activation and silencing methods have been employed to investigate the consequences of this lateralization for synaptic physiology and circuit organization during learning. The results suggest two general conclusions. First, the spatiotemporal precision of optogenetic tools enables the dissection of lateralization of circuit function in unprecedented detail. Second, seemingly subtle molecular and subcellular lateralizations can translate into prominent differences in circuit function across the hemispheres.

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Optogenetic Methods to Study Lateralized Synaptic Function

A fundamental unresolved problem in neuroscience is how the brain associates in memory events that are separated in time. Here we propose that reactivation-induced synaptic plasticity can solve this problem. Previously, we reported that the reinforcement signal dopamine converts hippocampal spike timing-dependent depression into potentiation during continued synaptic activity (Brzosko et al., 2015). Here, we report that postsynaptic bursts in the presence of dopamine produces input-specific LTP in hippocampal synapses 10 minutes after they were primed with coincident pre- and postsynaptic activity. The priming activity sets an NMDAR-dependent silent eligibility trace which, through the cAMP-PKA cascade, is rapidly converted into protein synthesis-dependent synaptic potentiation, mediated by a signaling pathway distinct from that of conventional LTP. Incorporated into a computational model, this synaptic learning rule adds specificity to reinforcement learning by controlling memory allocation and enabling both ‘instructive’ and ‘supervised’ reinforcement learning. We predicted that this mechanism would make reactivated neurons activate more strongly and carry more spatial information than non-reactivated cells, which was confirmed in freely moving mice performing a reward-based navigation task.

Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs

To survive, animals have to quickly modify their behaviour when the reward changes. The internal representations responsible for this are updated through synaptic weight changes, mediated by certain neuromodulators conveying feedback from the environment. In previous experiments, we discovered a form of hippocampal Spike-Timing-Dependent-Plasticity (STDP) that is sequentially modulated by acetylcholine and dopamine. Acetylcholine facilitates synaptic depression, while dopamine retroactively converts the depression into potentiation. When these experimental findings were implemented as a learning rule in a computational model, our simulations showed that cholinergic-facilitated depression is important for reversal learning. In the present study, we tested the model's prediction by optogenetically inactivating cholinergic neurons in mice during a hippocampus-dependent spatial learning task with changing rewards. We found that reversal learning, but not initial place learning, was impaired, verifying our computational prediction that acetylcholine-modulated plasticity promotes the unlearning of old reward locations. Further, differences in neuromodulator concentrations in the model captured mouse-by-mouse performance variability in the optogenetic experiments. Our line of work sheds light on how neuromodulators enable the learning of new contingencies.

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Ole Paulsen

Papers

Cholinergic suppression of sharp wave-ripples impairs hippocampus-dependent spatial memory

Optogenetic Methods to Study Lateralized Synaptic Function

Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs

The functional role of sequentially neuromodulated synaptic plasticity in behavioural learning.

Neuronal Mechanisms of Memory Formation: Synaptic Potentiation by Natural Patterns of Activity in the Hippocampus: Implications for Memory Formation