▪ 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

This book explains the relationship of electrophysiology, nonlinear dynamics, and the computational properties of neurons, with each concept presented in terms of both neuroscience and mathematics and illustrated using geometrical intuition In order to model neuronal behavior or to interpret the results of modeling studies, neuroscientists must call upon methods of nonlinear dynamics This book offers an introduction to nonlinear dynamical systems theory for researchers and graduate students in neuroscience It also provides an overview of neuroscience for mathematicians who want to learn the basic facts of electrophysiology "Dynamical Systems in Neuroscience" presents a systematic study of the relationship of electrophysiology, nonlinear dynamics, and computational properties of neurons It emphasizes that information processing in the brain depends not only on the electrophysiological properties of neurons but also on their dynamical properties The book introduces dynamical systems starting with one- and two-dimensional Hodgkin-Huxley-type models and continuing to a description of bursting systems Each chapter proceeds from the simple to the complex, and provides sample problems at the end The book explains all necessary mathematical concepts using geometrical intuition; it includes many figures and few equations, making it especially suitable for non-mathematicians Each concept is presented in terms of both neuroscience and mathematics, providing a link between the two disciplines Nonlinear dynamical systems theory is at the core of computational neuroscience research, but it is not a standard part of the graduate neuroscience curriculum - or taught by math or physics department in a way that is suitable for students of biology This book offers neuroscience students and researchers a comprehensive account of concepts and methods increasingly used in computational neuroscience

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Dynamical Systems in Neuroscience

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Calbindin D-28k and parvalbumin in the rat nervous system

Synchronous rhythms represent a core mechanism for sculpting temporal coordination of neural activity in the brain-wide network. This review focuses on oscillations in the cerebral cortex that occur during cognition, in alert behaving conditions. Over the last two decades, experimental and modeling work has made great strides in elucidating the detailed cellular and circuit basis of these rhythms, particularly gamma and theta rhythms. The underlying physiological mechanisms are diverse (ranging from resonance and pacemaker properties of single cells to multiple scenarios for population synchronization and wave propagation), but also exhibit unifying principles. A major conceptual advance was the realization that synaptic inhibition plays a fundamental role in rhythmogenesis, either in an interneuronal network or in a reciprocal excitatory-inhibitory loop. Computational functions of synchronous oscillations in cognition are still a matter of debate among systems neuroscientists, in part because the notion of regular oscillation seems to contradict the common observation that spiking discharges of individual neurons in the cortex are highly stochastic and far from being clocklike. However, recent findings have led to a framework that goes beyond the conventional theory of coupled oscillators and reconciles the apparent dichotomy between irregular single neuron activity and field potential oscillations. From this perspective, a plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention. Finally, implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.

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Neurophysiological and Computational Principles of Cortical Rhythms in Cognition

Monoclonal antibody mab-zebrin II was generated against a crude homogenate of cerebellum and electrosensory lateral line lobe from the weakly electric fish Apteronotus leptorhynchus. On Western blots of fish cerebellar proteins, mab-zebrin II recognizes a single polypeptide antigen of apparent molecular weight 36 kD. Immunocytochemistry of apteronotid brains reveals that zebrin II immunoreactivity is confined exclusively to Purkinje cells in the corpus cerebelli, lateral valvula cerebelli, and the eminentia granularis anterior. Other Purkinje cells, in the medial valvula cerebelli and eminentia granularis posterior, are not zebrin II immunoreactive. Immunoreactive Purkinje cells are stained completely, including dendrites, axons, and somata. The antigen seems to be absent only from the nucleus. A similar distribution is seen in catfish, goldfish, and a mormyrid fish. Zebrin II immunoreactivity is also found in the rat cerebellum. Western blotting of rat cerebellar proteins reveals a single immunoreactive polypeptide, with apparent, molecular weight 36 kD, as in the fish. Also as in the fish, staining in the adult rat cerebellum is confined to a subset of Purkinje cells. Peroxidase reaction product is deposited throughout the immunoreactive Purkinje cells with the exception of the nucleus. No other cells in the cerebellum express zebrin II. At higher antibody concentrations, a weak glial cross reactivity is seen in most other brain regions: we believe that this is probably nonspecific. Zebrin II+ Purkinje cells are clustered together to form roughly parasagittal bands interposed by similar non-immunoreactive clusters. In all there are 7 zebrin II+ and 7 zebrin II− compartments in each hemicerebellum. One immunoreactive band is adjacent to the midline; two others are disposed laterally to each side in the vermis; there is a paravermal band; and finally three more bands are identified in each hemisphere. Both in number and position, these compartments correspond precisely to the bands revealed by using another antibody, mabQ113 (anti-zebrin I). In both fish and rat the compartmentation revealed by zebrin II immunocytochemistry is related to the organization of cerebellar afferent and efferent projections and may provide clues as to the fundamental architecture of the vertebrate cerebellum.

Zebrin II: a polypeptide antigen expressed selectively by Purkinje cells reveals compartments in rat and fish cerebellum.

The steroid hormone, 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) causes the de novo synthesis of a calcium-binding protein (D-CaBP)1,2 This protein is present in highest concentrations in intestine, kidney and shell gland, across which calcium is transported in relatively large amounts, but it is also found in smaller amounts in several other tissues, including brain3–7 The area of brain with the highest D-CaBP concentration is the cerebellum, where the protein is found only in the Purkinje cells7,8 We have now mapped D-CaBP immuno-histochemically throughout the brain of chicks and rats and present here a list of all positive nuclei Because certain of these neurones also contain 1,25-(OH)2D3 (ref 9), we suggest that they are target cells for this hormone, thus broadening the functional significance of vitamin D to include the brain and implicating vitamin D in a more widespread action than simply a role in the calcium translocation mechanism of epithelial cells

Immunohistochemical mapping of vitamin D-dependent calcium-binding protein in brain

An atlas of the brain of the electric fish Apteronotus leptorhynchus.

The posterior lateral line lobe of two high-frequency weakly electric fish, Apteronotus albifrons and Eingenmannia viriscens, was studied at the electron microscopic level. The various cell types previously described by light microscopy (Maler, ′79) were identified on the basis of their unique position or by combined Golgi-EM. Afferent input to the posterior lobe was identified either by its location and generally accepted characteristics, e.g., parallel fibers in the molecular layer, or by making appropriate lesions and noting the degenerating terminals, e.g., primary electroreceptive afferents.



The major cell types of the posterior lobe are as follows: (1) spherical cells—an electron-dense cytoplasm crowded with ribosomes and other organelles; (2) granule cells—a small pale soma; fairly electron-dense dendrites, and pale axon terminals with clustered pleomorphic vesicles; (3) pyramidal cells—a large pale soma with a well-developed golgi apparatus; pale dendrites with evenly distributed microtubules; the somatic dendrites of pyramidal cells have an exceptional quantity of coated vesicles, multivesicular bodies, and smooth endoplasmic reticulum; (4) polymorphic cells—a medium-sized electron-dense soma; the dendrites are easily recognized by their content of neurofilaments, while their axon terminals are distinguished by their increased electron density and tightly packed ovoid vesicles.



Two types of primary electroreceptive afferents were identified: (1) Latency coder terminals were slightly electron-dense, with a small number of vesicles but large numbers of mitochondria; (2) Probability coder terminals were electron-lucent, with a large number of round synaptic vesicles; the diameters of these vesicles were always bimodally distributed. Afferent fibers to the molecular layer of the posterior lobe are organized as parallel fibers at the light microscopic level; ultrastructurally they are similar to parallel fibers of the cerebellum and make appropriate asymetric synapses on all apical dendritic trees within the molecular layer.



The circuitry of the posterior lobe is summarized in Figure 17. Latency coders make gap junction contact only with spherical cells, which in turn receive strictly latency coder input. Probability coders make mostly asymmetric chemical synapses onto granule cell and pyramidal cell basilar dendrites. The granule cell axons make symmetric synaptic contacts with the somata and somatic dendrites of both basilar and non-basilar pyramids; they also synapse on the ascending apical and basilar dendritic processes of granule cells. These ascending processes of granule cells make gap junction contacts with the somata and somatic dendrites of only the non-basilar pyramids. The consequence of this basic circuit appears to be that the posterior lobe can detect and enhance the contrast of objects with either high conductivity (basilar pyramids) or low conductivity (non-basilar pyramids).



The somatic dendrites of pyramidal cells were found to have extraordinary numbers of coated vesicles, and these were often associated with the postsynaptic densities of granule cell axons. The possible role of these coated vesicles in receptor recycling is discussed.



All afferents of the posterior lobe end in specific laminae, and in a given lamina they usually terminate on all potential postsynaptic sites; this was defined as laminar specificity of synaptic connections. The latency coder to spherical cells contacts, and the granule cell ascending process to non-basilar pyramid contacts are both specific to particular cells within a lamina; this was defined as cellular specificity of synaptic connections. Other examples of both sorts of synaptic specificity are presented and discussed in relation to current concepts of neuronal development.

The cytology of the posterior lateral line lobe of high-frequency weakly electric fish (Gymnotidae): dendritic differentiation and synaptic specificity in a simple cortex

Accurate detection of sensory input is essential for the survival of a species. Weakly electric fish use amplitude modulations of their self-generated electric field to probe their environment. P-type electroreceptors convert these modulations into trains of action potentials. Cumulative relative refractoriness in these afferents leads to negatively correlated successive interspike intervals (ISIs). We use simple and accurate models of P-unit firing to show that these refractory effects lead to a substantial increase in the animal's ability to detect sensory stimuli. This assessment is based on two approaches, signal detection theory and information theory. The former is appropriate for low-frequency stimuli, and the latter for high-frequency stimuli. For low frequencies, we find that signal detection is dependent on differences in mean firing rate and is optimal for a counting time at which spike train variability is minimal. Furthermore, we demonstrate that this minimum arises from the presence of negative ISI correlations at short lags and of positive ISI correlations that extend out to long lags. Although ISI correlations might be expected to reduce information transfer, in fact we find that they improve information transmission about time-varying stimuli. This is attributable to the differential effect that these correlations have on the noise and baseline entropies. Furthermore, the gain in information transmission rate attributable to correlations exhibits a resonance as a function of stimulus bandwidth; the maximum occurs when the inverse of the cutoff frequency of the stimulus is of the order of the decay time constant of refractory effects. Finally, we show that the loss of potential information caused by a decrease in spike-timing resolution is smaller for low stimulus cutoff frequencies than for high ones. This suggests that a rate code is used for the encoding of low-frequency stimuli, whereas spike timing is important for the encoding of high-frequency stimuli.

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Leonard Maler

Papers

Zebrin II: a polypeptide antigen expressed selectively by Purkinje cells reveals compartments in rat and fish cerebellum.

Immunohistochemical mapping of vitamin D-dependent calcium-binding protein in brain

An atlas of the brain of the electric fish Apteronotus leptorhynchus.

The cytology of the posterior lateral line lobe of high-frequency weakly electric fish (Gymnotidae): dendritic differentiation and synaptic specificity in a simple cortex

Negative Interspike Interval Correlations Increase the Neuronal Capacity for Encoding Time-Dependent Stimuli