Advances in Neural Signal Processing

Neural signal processing is a specialized area of signal processing aimed at extracting information or decoding intent from neural signals recorded from the central or peripheral nervous system. This has significant applications in the areas of neuroscience and neural engineering. These applications are famously known in the area of brain–machine interfaces. This book presents recent advances in this flourishing field of neural signal processing with demonstrative applications

Advances in Neural Signal Processing

Neural signal processing is a specialized area of signal processing aimed at extracting information or decoding intent from neural signals recorded from the central or peripheral nervous system. This has significant applications in the areas of neuroscience and neural engineering. These applications are famously known in the area of brain–machine interfaces. This book presents recent advances in this flourishing field of neural signal processing with demonstrative applications

Advances in Neural Signal Processing

Neural signal processing is a specialized area of signal processing aimed at extracting information or decoding intent from neural signals recorded from the central or peripheral nervous system. This has significant applications in the areas of neuroscience and neural engineering. These applications are famously known in the area of brain–machine interfaces. This book presents recent advances in this flourishing field of neural signal processing with demonstrative applications

FAD-Linked Autofluorescence and Chemically-Evoked Zinc Changes at Hippocampal Mossy Fiber-CA3 Synapses

Glutamatergic vesicles in hippocampal mossy fiber presynaptic boutons release zinc, which plays a modulatory role in synaptic activity and LTP. In this work, a fluorescence microscopy technique and the fluorescent probe for cytosolic zinc, Newport Green (NG), were applied, in a combined study of autofluorescence and zinc changes at the hippocampal mossy fiber-CA3 synaptic system. In particular, the dynamics of flavoprotein (FAD) autofluorescence signals, was compared to that of postsynaptic zinc signals, elicited both by high K+ (20 mM) and by tetraethylammonium (TEA, 25 mM). The real zinc signals were obtained subtracting autofluorescence values, from corresponding total NG-fluorescence data. Both autofluorescence and zinc-related fluorescence were raised by high K+. In contrast, the same signals were reduced during TEA exposure. It is suggested that the initial outburst of TEA-evoked zinc release might activate ATP-sensitive K+ (KATP) channels, as part of a safeguard mechanism against excessive glutamatergic action. This would cause sustained inhibition of zinc signals and a more reduced mitochondrial state. In favor of the “KATP channel hypothesis”, the KATP channel blocker tolbutamide (250 μM) nearly suppressed the TEA-evoked fluorescence changes. It is concluded that recording autofluorescence from brain slices is essential for the accurate assessment of zinc signals and actions

Effect of GABAA Receptor Clustering on Phasic and Tonic Inhibition in the Hippocampus

Inhibitory transmission plays a major role in information processing in the brain since it integrates excitatory signals and defines the gain between neural input and output. \u3b3-Amino butyric acid (GABA) is the main inhibitory neurotransmitter in the adult mammalian brain. By activating GABAA and GABAB receptors this neurotransmitter inhibits neuronal firing and stabilizes the membrane potential near the resting value. In particular GABAA receptors are permeable to chloride ions and are responsible for phasic and tonic hyperpolarizing responses. GABA-mediated currents are the result of rapid, sequential events including transmitter release from the presynaptic terminal, transmitter diffusion within and outside the cleft and post-synaptic receptors gating. The kinetics of each of these processes is crucial in determining the shape of post-synaptic currents. Therefore the modulation of any of these events leads to the heterogeneity of GABAergic responses and to changes in the potency of inhibition. In this thesis I have studied the sources of such variability at presynaptic/cleft and postsynaptic level. At presynaptic/cleft level I have focused on the influence of the agonist concentration profile in the synaptic cleft on GABA-mediated synaptic currents. Fast-off competitive antagonists and computer simulations allowed estimating the range of variability of the peak concentration and the speed of GABA clearance form the synaptic cleft. At postsynaptic level particular attention has been attributed to the impact of GABAA receptors clustering on both phasic and tonic GABAA-mediated inhibition. With ultrafast applications of GABA and computer simulations it was possible to describe the modulation of GABAA receptor gating induced by clustering

An electrophysical study of synaptic glutamate receptors in cerebellar golgi cells during development

N-methyl-D-aspartate receptors (NMDARs) are assemblies of NR1 and NR2 (NR2A-2D) subunits and their kinetic and pharmacological properties depend on the NR2 subunits expressed. We examined developmental changes in NMDAR- mediated excitatory postsynaptic currents (EPSCs) in mouse cerebellar Golgi cells in acute thin slices. Further, we investigated whether NMDAR subtypes are differentially distributed at synaptic and extrasynaptic sites. EPSCs were recorded under whole-cell voltage-clamp. EPSC decay kinetics and pharmacology were studied at postnatal days (P)7-8 and P15-18. We found EPSCs at P7-8 to be highly sensitive to the NR2B-selective antagonist ifenprodil. At P15-18, EPSCs were shorter in duration, less ifenprodil-sensitive but more sensitive to TPEN, an agent affecting NR2A-NMDARs. Taken together, these observations suggest a developmental switch from NR2B- to NR2A-NMDARs. We next examined whether similar changes occur extrasynaptically. Extrasynaptic NMDARs, activated by a high-frequency train of stimuli, were compared with synaptic NMDARs activated by a single stimulus. Single- and trains of EPSCs at P7-8 were highly ifenprodil-sensitive, suggesting NR2B-NMDARs are present both synaptically and extrasynaptically. At P15-18, train-generated EPSCs were slower and more ifenprodil-sensitive than single EPSCs. Ifenprodil sensitivity was further increased after blockade of synaptic NMDARs with the channel-blocker MK801. This supports the idea that the NR2B-to-NR2A switch is restricted to the synapse. NR2D-containing NMDARs are present on the soma of Golgi cells. To investigate whether NR2D-NMDARs are involved in synaptic transmission, we compared EPSCs from wild-type and NR2D-ablated mice at P7-10. We found no apparent differences in EPSC properties, suggesting NR2D is restricted to extrasynaptic sites. In conclusion, cerebellar Golgi cells express several NMDAR subtypes which are differentially distributed within the cell and developmentally regulated. At P7-8, NR2B-receptors are present at and peripheral to the synapse and NR2D-receptors are in the soma. By P15-18, NR2A-NMDARs are targeted to synapses while NMDARs in the vicinity remain of the NR2B subtype

Hippocampus

The hippocampus is a bicortical structure with extensive fiber connections with multiple brain regions. It is involved in several functions, such as learning, memory, attention, emotion, and more. This book covers various aspects of the hippocampus including cytoarchitecture, functions, diseases, and treatment. It highlights the most advanced findings in research on the hippocampus. It discusses circuits, pattern formation process of grid cells, and zinc dynamics of the hippocampus. The book also addresses the tau pathology and circRNAs related to Alzheimer’s disease and potential treatment strategies. It is a useful resource for general readers, students, and researchers

GABA_A-mediated synaptic activity in rat hippocampal neurones <i>in vitro</i> and its modulation by other neurotransmitters and second messengers.

The patch-clamp technique (whole-cell and outside-out configurations) has been used to characterize spontaneous ɣ-aminobutyric acid A (GABAA) receptor mediated currents in pyramidal cells of thin hippocampal slices obtained from neonatal rats. In early postnatal life, GABA is the main excitatory neurotransmitter on hippocampal pyramidal cells. The frequency distribution histogram of spontaneous GABAergic currents could be fitted by a single exponential function revealing the random nature of these events. The present results demonstrate that in tetrodotoxin (TTX) solution spontaneous GABAA receptor mediated miniature postsynaptic currents (mPSCs) were present. At -70 mV the first peak in the current amplitude distribution was 16 ± 6 pA (n =13). This value was similar to that found for GABAergic currents (14 ± 6 pA) elicited by low intensity extracellular stimulation, suggesting that this effect was due to the release of elementary units of GABA. In outside-out patches, GABA activated single-channel events of 24 and 35 pS conductance. Assuming that a postsynaptic current of 15 pA corresponds to a single quantum of GABA, one could calculate that one quantal current represents the simultaneous opening of 6 to 9 GABAA receptor channels in the postsynaptic cell. The metabotropic Glutamate Receptor (mGluR) agonist, 1 -aminocyclopentane-1,3-dicarboxylic acid (t-ACPD), induced an increase in frequency but not in amplitude of spontaneously occurring GABAergic currents; this potentiating effect was blocked by the Protein Kinase A (PKA) antagonist Rp-adenosine 3', 5'-cyclic monophosphotioate triethylamine (Rp-cAMPS), suggesting that glutamate, acting on mGluRs, is able to increase GABA release through the metabolic pathway which involves PKA. The potentiating effect of t-ACPD was not observed in TTX solution indicating that the site of action of the mGluR agonist is probably located at the somatodendritic level and not on the nerve terminals ofGABAergic intemeurones. In the presence of forskolin, which increases intracellular cyclic AMP (cAMP) levels, a rise in frequency but not in amplitude of miniature GABAA receptor mediated currents was observed, an effect that was prevented by the selective PKA antagonist Rp-cAMPS. These experiments suggest that presynaptic mGluRs localized on GABAergic interneurones may facilitate the activity of these cells and their release of GABA through cAMP-dependent PKA. Moreover, PKA may interfere directly with the mechanism of GABA release as demonstrated by its action on miniature events. The present results provide new evidence that the release of a major neurotransmitter such as GABA is up-regulated by another neurotransmitter namely Glutamate, thus demonstrating an important reinforcement of excitatory signals during an early stage of brain development

Modulation of synaptic transmission by interacting proteins and transporters

The properties of synaptic transmission may be modulated by transporters which regulate neurotransmitter and ion concentrations, and by proteins which interact with ion channels and transporters. I have investigated this for inhibitory and excitatory synapses in the retina and the cerebellum, using electrophysiological (patch-clamp) techniques. For inhibitory synaptic transmission, I have (1) discovered that GABAC receptors in retinal bipolar cells are modulated by the intracellular cytoskeletal protein MAP-1B, and shown that disrupting the interaction between MAP-1B and the GABAC receptor increases the sensitivity of the receptor to GABA, which is expected to alter the duration of the inhibitory postsynaptic current in these cells; and (2) studied the possibility that chloride transporters maintain a non-uniform intracellular chloride distribution in retinal bipolar cells, which determines the direction and magnitude of the GABA evoked membrane potential changes in the cell. For excitatory synaptic transmission I have (1) studied glutamatergic synaptic transmission in the cerebellum of transgenic mice lacking either of the glutamate transporters GLT-1 or GLAST, and demonstrated that GLAST knockout prolongs the synaptic current at the parallel fibre to Purkinje cell synapse, but that knocking out GLT-1 or GLAST does not alter the mossy fibre to granule cell synaptic current; (2) studied the effect of glycine on mossy fibre to granule cell synaptic transmission in the cerebellum of the rat, showing that the NMDA receptor glycine site is saturated even when no glycine is added to the superfusing solution; and (3) studied the properties of the LIM protein Ajuba, which interacts with the major glial glutamate transporter GLT-1, and shown that Ajuba does not modulate the transporter's glutamate sensitivity, its associated anion channel, or the number of transporters in the plasma membrane