Biomedical subjects

Kevin M Franks

Publications and source records attributed to Kevin M Franks.

5 recordsLinked to original sources

PubMed2006

Strong single-fiber sensory inputs to olfactory cortex: implications for olfactory coding.

Olfactory information is first encoded in a combinatorial fashion by olfactory bulb glomeruli, which individually represent distinct chemical features of odors. This information is then transmitted to piriform (olfactory) cortex, via axons of olfactory bulb mitral and tufted (M/T) cells, where it is presumed to form the odor percept. However, mechanisms governing the integration of sensory information in mammalian olfactory cortex are unclear. Here we show that single M/T cells can make powerful connections with cortical pyramidal cells, and coincident input from few M/T cells is sufficient to elicit spike output. These findings suggest that odor coding is broad and distributed in olfactory cortex.

Action Potentials↗

PubMed2005

Synapse-specific downregulation of NMDA receptors by early experience: a critical period for plasticity of sensory input to olfactory cortex.

Olfaction is required at birth for survival; however, little is known about the maturation of olfactory cortical circuits. Here we show that in vivo sensory experience mediates the development of excitatory transmission in pyramidal neurons of rat olfactory cortex. We find a postnatal critical period during which there is an experience-dependent increase in the contribution of AMPARs versus NMDARs to transmission at primary sensory synapses but not associational inputs. The shift in receptors underlying transmission is mediated by a strong activity-dependent downregulation of NMDARs and modest increase in AMPARs. Sensory activity leads to a loss of "silent" NMDAR-only synapses and an increase in threshold for inducing long-term plasticity. These results indicate the importance of early olfactory experience in the establishment of cortical circuits and could reflect mechanisms governing early olfactory "imprinting."

Aging↗

PubMed2003

Independent sources of quantal variability at single glutamatergic synapses.

Variability in the size of single postsynaptic responses is a feature of most central neurons, although the source of this variability is not completely understood. The dominant source of variability could be either intersynaptic or intrasynaptic. To quantitatively examine this question, a biophysically realistic model of an idealized central axospinous synapse was used to assess mechanisms underlying synaptic variability measurements. Three independent sources of variability were considered: stochasticity of postsynaptic receptors ("channel noise"), variations of glutamate concentration in the synaptic cleft (Deltaq), and differences in the potency of vesicles released from different locations on the active zone [release-location dependence (RLD)]. As expected, channel noise was small (8% of the total variance) and Deltaq was the dominant source of variability (58% of total variance). Surprisingly, RLD accounted for a significant amount of variability (36%). Our simulations show that potency of release sites decreased with a length constant of approximately 100 nm, and that receptors were not activated by release events >300 nm away, which is consistent with the observation that single active zones are rarely >300 nm. RLD also predicts that the manner in which receptors are added or removed from synapses can dramatically affect the nature of the synaptic response, with increasing receptor density being more efficient than merely increasing synaptic area. Saturation levels and synaptic geometry were also important in determining the size and shape of the distribution of amplitudes recorded at different synapses.

Biophysics↗

PubMed2002

Complexity of calcium signaling in synaptic spines.

Long-term potentiation and long-term depression are thought to be cellular mechanisms contributing to learning and memory. Although the physiological phenomena have been well characterized, little consensus of their underlying molecular mechanisms has emerged. One reason for this may be the under-appreciated complexity of the signaling pathways that can arise if key signaling molecules are discretely localized within the synapse. Recent findings suggest an unanticipated degree of structural organization at the synapse, and improved methods in cellular imaging of living tissue have provided much-needed information about the intracellular dynamics of Ca(2+), thought to be critical for both LTP and LTD. In this review, we briefly summarize some of these developments, and show that a more complete understanding of cellular signaling depends on the successful integration of traditional biochemistry and molecular biology with the spatial and temporal details of synaptic ultrastructure. Biophysically realistic computer simulations can have an important role in bridging these disciplines.

Animals↗

PubMed2002

A Monte Carlo model reveals independent signaling at central glutamatergic synapses.

We have developed a biophysically realistic model of receptor activation at an idealized central glutamatergic synapse that uses Monte Carlo techniques to simulate the stochastic nature of transmission following release of a single synaptic vesicle. For the a synapse with 80 AMPA and 20 NMDA receptors, a single quantum, with 3000 glutamate molecules, opened approximately 3 NMDARs and 20 AMPARs. The number of open receptors varied directly with the total number of receptors, and the fraction of open receptors did not depend on the ratio of co-localized AMPARs and NMDARs. Variability decreased with increases in either total receptor number or quantal size, and differences between the variability of AMPAR and NMDAR responses were due solely to unequal numbers of receptors at the synapse. Despite NMDARs having a much higher affinity for glutamate than AMPARs, quantal release resulted in similar occupancy levels in both receptor types. Receptor activation increased with number of transmitter molecules released or total receptor number, whereas occupancy levels were only dependent on quantal size. Tortuous diffusion spaces reduced the extent of spillover and the activation of extrasynaptic receptors. These results support the conclusion that signaling is spatially independent within and between central glutamatergic synapses.

Animals↗