Biomedical subjects

Leif Gibb

Publications and source records attributed to Leif Gibb.

5 recordsLinked to original sources

PubMed2005

Synaptic plasticity with discrete state synapses.

Experimental observations on synaptic plasticity at individual glutamatergic synapses from the CA3 Shaffer collateral pathway onto CA1 pyramidal cells in the hippocampus suggest that the transitions in synaptic strength occur among discrete levels at individual synapses [C. C. H. Petersen, Proc. Natl. Acad. Sci. USA 85, 4732 (1998); O'Connor, Wittenberg, and Wang, D. H. O'Connor, Proc. Natl. Acad. Sci. USA (to be published); J. M. Montgomery and D. V. Madison, Trends Neurosci. 27, 744 (2004)]. This happens for both long term potentiation (LTP) and long term depression (LTD) induction protocols. O'Connor, Wittenberg, and Wang have argued that three states would account for their observations on individual synapses in the CA3-CA1 pathway. We develop a quantitative model of this three-state system with transitions among the states determined by a competition between kinases and phosphatases shown by D. H. O'Connor, to be determinant of LTP and LTD, respectively. Specific predictions for various plasticity protocols are given by coupling this description of discrete synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor ligand gated ion channel conductance changes to a model of postsynaptic membrane potential and associated intracellular calcium fluxes to yield the transition rates among the states. We then present various LTP and LTD induction protocols to the model system and report the resulting whole cell changes in AMPA conductance. We also examine the effect of our discrete state synaptic plasticity model on the synchronization of realistic oscillating neurons. We show that one-to-one synchronization is enhanced by the plasticity we discuss here and the presynaptic and postsynaptic oscillations are in phase. Synaptic strength saturates naturally in this model and does not require artificial upper or lower cutoffs, in contrast to earlier models of plasticity.

Action Potentials↗

PubMed2004

Dynamical model of birdsong maintenance and control.

The neuroethology of song learning, production, and maintenance in songbirds presents interesting similarities to human speech. We have developed a biophysical model of the manner in which song could be maintained in adult songbirds. This model may inform us about the human counterpart to these processes. In songbirds, signals generated in nucleus High Vocal center (HVc) follow a direct route along a premotor pathway to the robust nucleus of the archistriatum (RA) as well as an indirect route to RA through the anterior forebrain pathway (AFP): the neurons of RA are innervated from both sources. HVc expresses very sparse bursts of spikes having interspike intervals of about 2 ms. The expressions of these bursts arrive at the RA with a time difference DeltaT approximately equal to 50+/-10 ms between the two pathways. The observed combination of AMPA and NMDA receptors at RA projection neurons suggests that long-term potentiation and long-term depression can both be induced by spike timing plasticity through the pairing of the HVc and AFP signals. We present a dynamical model that stabilizes this synaptic plasticity through a feedback from the RA to the AFP using known connections. The stabilization occurs dynamically and is absent when the RA-->AFP connection is removed. This requires a dynamical selection of DeltaT. The model does this, and DeltaT lies within the observed range. Our model represents an illustration of a functional consequence of activity-dependent plasticity directly connected with neuroethological observations. Within the model the parameters of the AFP, and thus the magnitude of DeltaT, can also be tuned to an unstable regime. This means that destabilization might be induced by neuromodulation of the AFP.

Action Potentials↗

PubMed2004

Spike timing and synaptic plasticity in the premotor pathway of birdsong.

The neural circuits of birdsong appear to utilize specific time delays in their operation. In particular, the anterior forebrain pathway (AFP) is implicated in an approximately 40- to 50- ms time delay, DeltaT, playing a role in the relative timing of premotor signals from the nucleus HVc to the nucleus robust nucleus of the archistratium (RA) and control/learning signals from the nucleus lateral magnocellular nucleus of the anterior neostratium (lMAN) to RA. Using a biophysical model of synaptic plasticity based on experiments on mammalian hippocampal and neocortical pyramidal neurons, we propose an understanding of this approximately 40- to 50- ms delay. The biophysical model describes the influence of Ca2+ influx into the postsynaptic RA cells through NMDA and AMPA receptors and the induction of LTP and LTD through complex metabolic pathways. The delay, DeltaT, between HVc --> RA premotor signals and lMAN --> RA control/learning signals plays an essential role in determining if synaptic plasticity is induced by signaling from each pathway into RA. If DeltaT is substantially larger than 40 ms, no plasticity is induced. If DeltaT is much less than 40 ms, only potentiation is expected. If DeltaT approximately 40 ms, the sign of synaptic plasticity is sensitive to DeltaT. Our results suggest that changes in DeltaT may influence learning and maintenance of birdsong. We investigate the robustness of this result to noise and to the removal of the Ca2+ contribution from lMAN --> RA NMDA receptors.

Action Potentials↗

PubMed2004

Mapping neural architectures onto acoustic features of birdsong.

The motor pathway responsible for the complex vocalizations of songbirds has been extensively characterized, both in terms of intrinsic and synaptic physiology in vitro and in terms of the spatiotemporal patterns of neural activity in vivo. However, the relationship between the neural architecture of the song motor pathway and the acoustic features of birdsong is not well understood. Using a computational model of the song motor pathway and the songbird vocal organ, we investigate the relationship between song production and the neural connectivity of nucleus HVc (used as a proper name) and the robust nucleus of the archistriatum (RA). Drawing on recent experimental observations, our neural model contains a population of sequentially bursting HVc neurons driving the activity of a population of RA neurons. An important focus of our investigations is the contribution of intrinsic circuitry within RA to the acoustic output of the model. We find that the inclusion of inhibitory interneurons in the model can substantially influence the features of song syllables, and we illustrate the potential for subharmonic behavior in RA in response to forcing by HVc neurons. Our results demonstrate the association of specific acoustic features with specific neural connectivities and support the view that intrinsic circuitry within RA may play a critical role in generating the features of birdsong.

Action Potentials↗

PubMed2003

Biophysical model of synaptic plasticity dynamics.

We discuss a biophysical model of synaptic plasticity that provides a unified view of the outcomes of synaptic modification protocols, including: (1) prescribed time courses of postsynaptic intracellular Ca(2+) release, (2) postsynaptic voltage clamping with presentation of presynaptic spike trains at various frequencies, (3) direct postsynaptic response to presynaptic spike trains at various frequencies, and (4) LTP/LTD as a response to precisely timed presynaptic and postsynaptic spikes.

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