Nicotine synapse formation in the hippocampus
Initial Award Abstract
The nicotine found in cigarette smoke and other forms of tobacco has an effect on the body by acting on naturally occurring components on neurons. These components are call nicotinic acetylcholine receptors because they normally bind the chemical acetylcholine in the brain and cause current to flow into the neuron, but they can also be activated by exogenous nicotine. Though such nicotinic receptors are found throughout the brain, little is known about how activation of these receptors affects communication between cells.
The hippocampus is an area of the brain that is essential for forming new memories. During the first few weeks of postnatal life, the hippocampus has a relatively high number of nicotinic receptors. One type they have in abundance is a nicotinic receptor that allows calcium to enter the cell. Because calcium can regulate many events in neurons, these receptors are particularly powerful. For example, calcium not only regulates electrical and chemical signaling in the neuron but can even turn genes on and off. When we look closely at neurons from the hippocampus, we find these receptors are often positioned at the tips of long narrow projections called filopodia. Filopodia comprise little compartments extending from the neuron. Calcium coming into these compartments may well have local effects that are important for how the cell establishes contacts with other neurons. The other components of these small filopodial compartments are likely to be affected by calcium as well.
The experiments that we are proposing focus on these nicotinic receptors. We will treat hippocampal neurons with different chemicals to determine how these receptors are regulated and where they are positioned. Different types of neurons work together in complex ways to create patterns of activity in the hippocampus. We hope to determine which of these cells are responsible for expressing high levels of the receptors so that we can predict the effects nicotine will have on hippocampal activity. We will look closely at how filopodia having the receptors participate in forming specific contacts between neurons. We will also study how the hippocampus develops if the receptors have been removed or are blocked. These experiments are especially relevant to how the hippocampus uses acetylcholine to form connections during development and how these connections change over time. A critical question is the how nicotine from cigarette smoke changes this natural course of development, both during fetal growth and at subsequent stages. By understanding how nicotine effects the connections within the brain, we will gain important new insights into the nature of normal communication between neurons. These experiments will also indicate the consequences of nicotine having perturbed the normal interactions and instructions that in effect guide early brain development. |
|BDNF up-regulates alpha7 nicotinic acetylcholine receptor levels on subpopulations of hippocampal interneurons.
|Periodical: Molecular and Cellular Neuroscience
|Authors: Massey KA, Zago WM, Berg DK.