I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

▪ Abstract Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemical synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks. This review focuses on synaptic changes that result from prior activity in the synapse under study, and is restricted to short-term effects that last for at most a few minutes. Forms of synaptic enhancement, such as facilitation, augmentation, and post-tetanic potentiation, are usually attributed to effects of a residual elevation in presynaptic [Ca2+]i, acting on one or more molecular targets that appear to be distinct from the secretory trigger responsible for fast exocytosis and phasic release of transmitter to single action potentials. We discuss the evidence for this hypothesis, and the origins of the different kinetic phases...

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Short-Term Synaptic Plasticity

The physiology of excitatory amino acids in the vertebrate central nervous system.

We tested a theoretical prediction that patterns of excitatory input activity that consistently fail to activate target neurons sufficiently to induce synaptic potentiation will instead cause a specific synaptic depression. To realize this situation experimentally, the Schaffer collateral projection to area CA1 in rat hippocampal slices was stimulated electrically at frequencies ranging from 0.5 to 50 Hz. Nine hundred pulses at 1-3 Hz consistently yielded a depression of the CA1 population excitatory postsynaptic potential that persisted without signs of recovery for greater than 1 hr after cessation of the conditioning stimulation. This long-term depression was specific to the conditioned input, ruling out generalized changes in postsynaptic responsiveness or excitability. Three lines of evidence suggest that this effect is accounted for by a modification of synaptic effectiveness rather than damage to or fatigue of the stimulated inputs. First, the effect was dependent on the stimulation frequency; 900 pulses at 10 Hz caused no lasting change, and at 50 Hz a synaptic potentiation was usually observed. Second, the depressed synapses continued to support long-term potentiation in response to a high-frequency tetanus. Third, the effects of conditioning stimulation could be prevented by application of NMDA receptor antagonists. Thus, our data suggest that synaptic depression can be triggered by prolonged NMDA receptor activation that is below the threshold for inducing synaptic potentiation. We propose that this mechanism is important for the modifications of hippocampal response properties that underlie some forms of learning and memory.

https://www.pnas.org/content/pnas/89/10/4363.full.pdf

Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade.

Although signaling between neurons is central to the functioning of the brain, we still do not understand how the code used in signaling depends on the properties of synaptic transmission. Theoretical analysis combined with patch clamp recordings from pairs of neocortical pyramidal neurons revealed that the rate of synaptic depression, which depends on the probability of neurotransmitter release, dictates the extent to which firing rate and temporal coherence of action potentials within a presynaptic population are signaled to the postsynaptic neuron. The postsynaptic response primarily reflects rates of firing when depression is slow and temporal coherence when depression is fast. A wide range of rates of synaptic depression between different pairs of pyramidal neurons was found, suggesting that the relative contribution of rate and temporal signals varies along a continuum. We conclude that by setting the rate of synaptic depression, release probability is an important factor in determining the neural code.

The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability

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

Axotomy-induced alterations in the electrophysiological characteristics of neurons

Transmission at a central inhibitory synapse. II. Quantal description of release, with a physical correlate for binomial n.

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, θ( t ), specifically κ( t ) = θ( t − δ × e −βθ(t − δ), where the exponential term progressively reduces the weight of θ( 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 κ( 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.

https://www.jneurosci.org/content/jneuro/26/13/3454.full.pdf

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

Synaptic events at the neuromuscular junction are integer multiples of a quantum, the postsynaptic response to transmitter released from one presynaptic vesicle. At central synapses where quanta are small, it has been suggested they are invariant due to occupation of all postsynaptic receptors, a concept neglecting inherent fluctuations in channel behavior. If this did occur, the quantal release model would not apply there and could not be used to localize sites of synaptic modification. Monte Carlo simulations of quanta include transmitter diffusion and interactions with postsynaptic receptors that are treated probabilistically. These models suggest that when there are few postsynaptic channels available at a synapse, their stochastic behavior produces significant intrinsic variance in response amplitude and kinetics, and saturation does not occur. These results were confirmed by analysis of inhibitory quanta in embryonic and adult Mauthner cells involving a small and large number of channels, respectively. The findings apply to excitatory synapses as well.

http://science.sciencemag.org/content/sci/258/5087/1494.full.pdf

Donald S. Faber

Papers

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

Axotomy-induced alterations in the electrophysiological characteristics of neurons

Transmission at a central inhibitory synapse. II. Quantal description of release, with a physical correlate for binomial n.

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

Intrinsic quantal variability due to stochastic properties of receptor-transmitter interactions.