Biomedical subjects

Sacha B Nelson

Publications and source records attributed to Sacha B Nelson.

26 records · Page 2Linked to original sources

PubMed2003

The NMDA-to-AMPA ratio at synapses onto layer 2/3 pyramidal neurons is conserved across prefrontal and visual cortices.

To better understand regulation of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor complements across the cortex, and to investigate NMDA receptor (NMDAR)-based models of persistent activity, we compared NMDA/AMPA ratios in prefrontal (PFC) and visual cortex (VC) in rat. Whole cell voltage-clamp responses were recorded in brain slices from layer 2/3 pyramidal cells of the medial PFC and VC of rats aged p16-p21. Mixed miniature excitatory postsynaptic currents (mEPSCs) having AMPA receptor (AMPAR)- and NMDAR-mediated components were isolated in nominally 0 Mg2+ ACSF. Averaged mEPSCs were well-fit by double exponentials. No significant differences in the NMDA/AMPA ratio (PFC: 27 +/- 1%; VC: 28 +/- 3%), peak mEPSC amplitude (PFC: 19.1 +/- 1 pA; VC: 17.5 +/- 0.7 pA), NMDAR decay kinetics (PFC: 69 +/- 8 ms; VC: 67 +/- 6 ms), or degree of correlation between NMDAR- and AMPAR-mediated mEPSC components were found between the areas (PFC: n = 27; VC: n = 28). Recordings from older rats (p26-29) also showed no differences. EPSCs were evoked extracellularly in 2 mM Mg2+ at depolarized potentials; although the average NMDA/AMPA ratio was larger than that observed for mEPSCs, the ratio was similar in the two regions. In nominally 0 Mg2+ and in the presence of CNQX, spontaneous activation of NMDAR increased recording noise and produced a small tonic depolarization which was similar in both areas. We conclude that this basic property of excitatory transmission is conserved across PFC and VC synapses and is therefore unlikely to contribute to differences in firing patterns observed in vivo in the two regions.

Animals↗

PubMed2002

Rate and timing in cortical synaptic plasticity.

Debate has raged over the past few years as to whether cortical neurons transmit information primarily in their average firing rates or in the precise timing of their spikes. Here, we address the related question of which features of spike trains control plasticity at cortical synapses. Using paired recording in slices we have developed a quantitative and predictive description of the joint dependence of cortical plasticity on the rate and relative timing of pre- and postsynaptic firing. The results hold important implications for which parts of the neural code are most readily stored for later retrieval.

Action Potentials↗

PubMed2002

Multi-unit spike-triggered averaging: a method for probing the physiology of central synapses.

We describe the ongoing development of a method that combines multi-unit extracellular recording with intracellular recording to probe unitary synaptic connections in the central nervous system. In multi-unit spike-triggered averaging (multi-unit STA), intracellular recordings are averaged based on extracellularly recorded action potentials from multiple units to rapidly screen large numbers of neuronal pairs for rare synaptic connections. High throughput is achieved by using many extracellular electrodes and online, automated analysis. Using this approach, we were able to screen dozens of candidate pairs per hour. About 1-2% of these were synaptically connected, and for some of these presynaptic unit isolation was sufficient to accurately quantify synaptic properties such as latency, conductance, kinetics and transmission failure rate. Since it requires only a single intracellular recording, multi-unit STA might be a suitable method for probing unitary synaptic connections in the intact brain, where obtaining multiple intracellular recordings is not feasible.

Algorithms↗

PubMed2002

Short-term depression at thalamocortical synapses contributes to rapid adaptation of cortical sensory responses in vivo.

In vivo whole-cell recordings revealed that during repeated stimulation, synaptic responses to deflection of facial whiskers rapidly adapt. Extracellular recordings in the somatosensory thalamus revealed that part of the adaptation occurs subcortically, but because cortical adaptation is stronger and recovers more slowly, cortical mechanisms must also contribute. Trains of sensory stimuli that produce profound sensory adaptation did not alter intrinsic membrane properties, including resting membrane potential, input resistance, and current-evoked firing. Synaptic input evoked via intracortical stimulation was also unchanged; however, synaptic input from the somatosensory thalamus was depressed by sensory stimulation, and this depression recovered with a time course matching that of the recovery of sensory responsiveness. These data strongly suggest that synaptic depression of thalamic input to the cortex contributes to the dynamic regulation of neuronal sensitivity during rapid changes in sensory input.

Adaptation, Physiological↗

PubMed2002

Fast propagation of firing rates through layered networks of noisy neurons.

We model the propagation of neural activity through a feedforward network consisting of layers of integrate-and-fire neurons. In the presence of a noisy background current and spontaneous background firing, firing rate modulations are transmitted linearly through many layers, with a delay proportional to the synaptic time constant and with little distortion. Single neuron properties and firing statistics are in agreement with physiological data. The proposed mode of propagation allows for fast computation with population coding based on firing rates, as is demonstrated with a local motion detector.

Computer Simulation↗

PubMed2002

Spike timing, calcium signals and synaptic plasticity.

Plasticity at central synapses depends critically on the timing of presynaptic and postsynaptic action potentials. Key initial steps in synaptic plasticity involve the back-propagation of action potentials into the dendritic tree and calcium influx that depends nonlinearly on the action potential and synaptic input. These initial steps are now better understood. In addition, recent studies of processes as diverse as gene expression and channel inactivation suggest that responses to calcium transients depend not only their amplitude, but on their time course and on the location of their origin.

Action Potentials↗

PubMed2002

Critical periods for experience-dependent synaptic scaling in visual cortex.

The mechanisms underlying experience-dependent plasticity and refinement of central circuits are not yet fully understood. A non-Hebbian form of synaptic plasticity, which scales synaptic strengths up or down to stabilize firing rates, has recently been discovered in cultured neuronal networks. Here we demonstrate the existence of a similar mechanism in the intact rodent visual cortex. The frequency of miniature excitatory postsynaptic currents (mEPSCs) in principal neurons increased steeply between post-natal days 12 and 23. There was a concomitant decrease in mEPSC amplitude, which was prevented by rearing rats in complete darkness from 12 days of age. In addition, as little as two days of monocular deprivation scaled up mEPSC amplitude in a layer- and age-dependent manner. These data indicate that mEPSC amplitudes can be globally scaled up or down as a function of development and sensory experience, and suggest that synaptic scaling may be involved in the activity-dependent refinement of cortical connectivity.

Aging↗

PubMedDate not supplied

The squirrel as a rodent model of the human visual system.

Over the last 50 years, studies of receptive fields in the early mammalian visual system have identified many classes of response properties in brain areas such as retina, lateral geniculate nucleus (LGN), and primary visual cortex (V1). Recently, there has been significant interest in understanding the cellular and network mechanisms that underlie these visual responses and their functional architecture. Small mammals like rodents offer many advantages for such studies, because they are appropriate for a wide variety of experimental techniques. However, the traditional rodent models, mice and rats, do not rely heavily on vision and have small visual brain areas. Squirrels are highly visual rodents that may be excellent model preparations for understanding mechanisms of function and disease in the human visual system. They use vision for navigating in their environment, predator avoidance, and foraging for food. Visual brain areas such as LGN, V1, superior colliculus, and pulvinar are particularly large and well elaborated in the squirrel, and the squirrel has several extrastriate cortical areas lateral to V1. Unlike many mammals, most squirrel species are diurnal with cone-dominated retinas, similar to the primate fovea, and have excellent dichromatic color vision that is mediated by green and blue cones. Owing to their larger size, squirrels are physiologically more robust than mice and rats under anesthesia, and some hibernating species are particularly tolerant of hypoxia that occurs during procedures such as brain slicing. Finally, many basic anatomical and physiological properties in the early visual system of squirrel have now been described, permitting investigations of cellular mechanisms. In this article, we review four decades of anatomical, behavioral, and physiological studies in squirrel and make comparisons with other species.

Animals↗