Genes, Brain Plasticity & Memory

The strengthening of connections between nerve cells in the cerebral cortex has been associated with the formation of dendritic spines, that is, small protrusions of the nerve arbors on which mostly excitatory endings of other nerve cells terminate. The endings are called synapses. The excitation is mediated by the neurotransmitter glutamate released at the synapses. The number of spines is dynamic. Spines decrease with prolonged deprivation of sensory input (Valverde, 1967) and increase with prolonged experience-dependent stimulation of sensory input (Knott and others, 2006). With advanced optical imaging methods, Hofer and others (2009) were able to examine the dynamics of dendritic spine changes in the same preparation. They observed that the occlusion of one eye in adult mice resulted in decreases and subsequent profound increases in spine density on apical dendrites of pyramidal cells in visual cortex. The increases were presumably associated with prevailing input from the intact eye. With repeated eye occlusion, the first deprivation led to a two-fold augmentation of the rate of spine development, resulting in a net increase in spine density. The latter remained elevated after binocular vision was restored and did not increase further after the same eye was occluded for a second time. The authors concluded that the persistent spines were pertinent to the experience of the first deprivation, providing perhaps a mechanism for a lasting memory trace.

In this week's issue of the journal Nature, Ji-Song Guan and others at the Picower Institute for Learning and Memory provide evidence that the gene Hdac2 plays a crucial role in spine and synapse formation in as much as in the enhancement of memory. Hdac2 encodes type 2 histone deacetylase. Histones are proteins that are attached to coiled DNA, regulating access to the genetic code. Histone deacetylases are enzymes that remove acetyl groups at the tails of histones. The authors report that overexpression of the gene in mice diminished spine density, decreased the number of synapses, and degraded memory. Inhibition of histone deacetylase 2 augmented synapse number and improved memory. Conversely, lack of Hdac2 enhanced the number of synapses, spine density and memory; treatment with histone deacetylase 2 inhibitors was ineffective. Furthermore, the authors established that other genes known to influence synaptic formation promote the expression of Hdac2. Hence, we have come one step closer to the understanding of the molecular mechanisms that underlie brain plasticity and memory.

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