Andrew & Patrick’s Neuroblog

2004 review of plasticity in Neuron 44, 30 Sept by Malenka and Bear.

* LTP and LTD play what functional roles in specific types of experience-dependent plasticity?
* clear that there are many forms of LTP and LTD and they share some but not all of the properties of NMDAR dependent LTP and LTD
* the question of whether LTP and LTD are used for memory is pretty much a moot point now
*mossy fiber LTP appears to be PKA-dependent, presynaptic in origin, and leads to an increased Pr (probability of neurotransmitter release). All presynaptic, as opposed to the postsynaptic NMDAR-dependent LTP
* NMDAR-dependent LTD: induced by low frequency stimulation
* requires actiation of a serine-threonine phosphatase cascade
* most of the work has been done in CA1
* mGluR-depenent LTD: can also be induced by long periods of 1 Hz pulses
* inhibition of NMDARs blocks LTD, actiation of NMDARs induces it
* one synaptic protein that appears to be a slot protein is PSD-95
* NmDAR activation leads to ubiquitination and degradation of PSD-95 - might act for LTD and to remove synapses (Mike Ehlers type of stuff)
* retrograde signaling by endogenous cannabinoids coincides with activation of presynaptic NMDARs?

Tips from Professor Sue McConnell of Stanford University:

Powerpoint design

• For small teaching classrooms, black text on white backgrounds work well
• For larger halls, light text on dark blue backgrounds work well
• don’t use red and green - large percentage of people are color blind!
• make sure the text is the appropriate size and sans serif - around 20-28 points large
• don’t clutter slides, 1 or 2 points per slide
• keep lists to maximum 3 points if possible
• build the slides when possible, make sure there is perfect harmony between your voice, visual aids, and text on the screen

General

• respect length of the talk
• don’t give false conclusions - like conclusion to just part 1, then you’re starting part 2! That’s bad!
• Keep in mind the “interest level” of the audience: higher in the beginning, dips down until the conclusion, where it goes back up
• start with general ideas, narrow it down to specific questions and data, and at the end broaden back to the bigger picture
• during the content of the talk, remember the “sawtooth” structure - go deep into data, then back up to a more shallow depth, then back down, and so on

1. Dendrite Self-Avoidance is controlled by Dscam (Cell 2007 from Wes Grueber’s lab)
This paper looks at the problem of dendrite self-avoidance, a critical process in development, in Drosophila sensory neurons. Dscam, a gene that has a vast number of isoforms formed by alternative splicing, has been shown to have an important role in self-recognition. Sister dendrites from the same neuron express the same isoform, resulting in homophilic repulsion that prevents dendrites from crossing. The neighboring neurons and their dendritic arbors all express different isoforms of Dscam that don’t result in inappopriate repulsion. Thus, this Dscam-mediated self avoidance seems to be a general developmental organization principle in Drosophila.

2. Dscam is a netrin receptor that collaborates with DCC in mediating turning responses to netrin-1 (Cell 2008 from Elke Stein’s lab)
Dscam again, but in this case it’s in the developmental nervous system of mouse spinal cord. For proper spinal cord development, axons have to cross the midline to form the commissure. This midline crossing is mediated by several chemoattractants and repellants. One important chemoattractant, netrin-1, is known to act through a netrin receptor DCC to attract axons toward the midline. Ly et al. have shown in this paper that Dscam is another netrin receptor that also helps the outgrowth and midline crossing. DCC appears to be more involved in axon outgrowth, while Dscam is more important for the turning response. Dscam is present in both Drosophila and mice, but there doesn’t seem to be any good homolog in humans, so I’m not sure how this could be translated.

3. Architecture and activity-mediated refinement of axonal projections from a mosaic of genetically identified retinal ganglion cells (Neuron 2008 from Ben Barres’ and Steve Baccus’ labs)
There are many different classes of retinal ganglion cells (RGCs) and Huberman et al. in this paper have found a mouse through screening a library of BAC transgenic mice that has specific GFP+ labeling in tOFF-aRGCs. The idea behind this paper is to investigate this specific class of cells, look at where they project, and how those projections are formed developmentally. These RGCs that are GFP+ have laminar-specific projections to both the dLGN (dorsal lateral geniculate nucleus) and the SC (superior colliculus). In the case of the SC, the projections are also columnarly organized. They showed that these projections are not laminarly restricted during development; the projections are nonspecific at first and then are refined by development. In fact, retinal waves are required to form proper columns in the SC, but not proper lamina, consistent with previous results on the formation of columns and layers.