Research in the Segal Lab

The following are highlights of some of our recent observations:

• We compared the ability of slices taken from the dorsal or ventral sectors of the hippocampus to express LTP. Much to our surprise, we were unable to produce LTP in the latter group (Maggio and Segal, 2007). However, exposing animals to acute swim stress increased LTP in ventral hippocampus, compared to its dorsal counterpart (Maggio and Segal 2007 JN). This could indicate that the two sectors may have different electrophysiological properties and functional relevance.

• Using paired recording in cultured hippocampal neurons we found that chemical conditioning (i.e. a momentary exposure of the culture to a NMDA-enhancing conditioning medium) can produce a lasting increase in excitatory synaptic connectivity among pairs of cultured neurons. More interestingly, we found that this treatment caused a lasting decrease in inhibitory connections among the cultured neurons. This persistent change in connectivity is caused by a presynaptic change in release properties of the inhibitory neuron (Ivenshitz and Segal, 2006).

• Using cultured cortical neurons, we found that spontaneous activity is crucial for the survival of these neurons in culture, and that long term blockade of activity results in degeneration of these neurons. Counter-intuitively, this degeneration can be blocked by antagonizing the glutamate receptor, indicating that spontaneous miniature excitatory synaptic currents can kill neurons (Fishbein and Segal, 2006). Interestingly, before they die, cortical neurons shed their dendritic spines, suggesting that the spines may have a protective role against neurodegeneration and that in their absence the neurons are more vulnerable.

• We found that exposure of cultured neurons to a conditioning medium causes influx of glutamate receptors (GluR1-eGFP) into dendritic spines. This influx was selective and affected only short spines. We further explored this phenomenon and found that flash photolysis of caged calcium in spine heads was sufficient to cause an influx of GluR1 molecules into the spine heads (Korkotian and Segal, 2006).

• We compared the ability of slices taken from the dorsal or ventral sectors of the hippocampus to express LTP. Much to our surprise, we were unable to produce LTP in the latter group, indicating that the two sectors may have different electrophysiological properties and functional relevance. We are in the process of further exploration of this difference and an attempt to relate different behavioral and electrophysiological functions to these two sectors of the hippocampus (Maggio and Segal, 2007).

• We found that a brief exposure of cultured neurons to glutamate can produce a long lasting suppression of activity, as well as resistance to later toxic insults. We are currently exploring the mechanisms underlying this long term effect.

These studies are planned to provide a link between the detailed structure and function of central neurons, in order to provide a better understanding of the role of dendritic spines in synaptic plasticity, learning and memory.