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CLIPPING VIVAVOZFonte: Guardian Seção: Página: Data: 02/03/2012 How marijuana impairs memory Marijuanas effects on memory are controlled by hitherto neglected brain cells called astrocytes Marijuana is well known to impair short-term memory. Photograph: Jockmans/Rex Features My latest news story for Nature describes a new study which explains how marijuana causes impairments in working memory, or the ability to retain information for short periods of time. This is a well known side effect of marijuana, which is unwanted with respect to medicinal use of the drug, but until now the underlying neurobiology was unknown. The research shows that tetrahydrocanabinol (THC, the psychoactive ingredient in marijuana) impairs working memory by inducing a form of synaptic plasticity that weakens neuronal connections. This could lead to new THC-related drugs that have therapeutic value but do not cause this unwanted effect. More interestingly, though, the findings provide compelling evidence that hitherto neglected brain cells called astrocytes are critical for brain function and play a direct role in cognitive processes. There are two different types of synapitc plasticity. One of these, called long-term potentiation, strengthens the connections between neurons so that neurotransmission – the process by which signals pass from one nerve cell to another – is more effective. Long-term potentiation is widely believed to underly learning and memory. The other form, called long-term depression, has the opposite effect – it makes connections weaker by reducing the efficacy of neurotransmission. The basic principles of neurotransmission are well understood. Nervous impulses travel along the nerve fibre until they reach the nerve terminal. The signals cannot cross synapses – the tiny junctions between neurons – so they are converted into a chemical
signal. At the terminal, neurotransmitter molecules are stored in spherical structurescalled vesicles, and the arrival of a nervous impulse causes these to fuse with theterminal membrane and release their contents into the synapse. The transmittermolecules then diffuse across the synapse and bind to receptors on the membrane ofthe neighbouring cell, causing it to generate its own nervous impulses.This process can be enhanced or diminished in a number of ways. The number ofvesicles that fuse with the terminal membrane, or the frequency with which thishappens, can both be increased, so that more transmitter molecules are released intothe synapse. Conversely, the number or frequency of these fusion events can bedecreased, so that fewer molecules are released. All of these processes are referred toas presynaptic, because they take place in the cell that transmits the signal.There are also postsynaptic mechanisms for altering the efficacy of transmission, whichoccur at the other side of the synapse in the cell that receives the signal. The effects ofneurotransmission are determined by the receptors which bind the transmittermolecules, so the strength of the signal can be modulated by altering the number ofreceptors in the membrane of the cell on the other side of the synapse.Receptor molecules are stored in pools located close to the membrane, and can beshuttled back and forth between these pools and the membrane. Thus, receptors canbe inserted into the membrane by the same fusion process which causesneurotransmitter release. They can also be removed by a reversal of the process, inwhich pieces of membrane are pulled into the cell.Long-term potentiation and memory formation are critically dependent on two types ofreceptor for the neurotransmitter glutamate, called NMDA and AMPA receptors. Thenew research shows that THC impairs working memory by inducing the removal ofAMPA receptors from the membranes of neurons in the hippocampus, a structureknown to be crucial for memory formation.Shuttling of AMPA receptors into and out of nerve cell membranes is well known tounderly long-term potentiation and depression, but the new study shows, for the firsttime, that removal of AMPA receptors from nerve cell membranes is controlled byastrocytes. They express a cannabinoid receptor which, when activated by THC, sendsa signal to neurons that initiates the process.Astrocytes are one of several types of glial cell found in the brain. The term glia meansglue in Greek, and reflects the long-standing view that these cells do little more thansupport, nourish and protect neurons.In recent years, however, it has become increasingly clear that astrocytes are far moreimportant than previously thought. We now know, for example, that they can sendsignals not only to each other but also to neurons. They can also regulateneurotransmission by clasping synapses with finger-like projections called endfeet.They even build blood vessel scaffolds that guide the migration of newborn neuronsAll of this suggests that astrocytes make a significant contribution to informationprocessing in the brain. Ever since their discovery more than a hundred years ago,these humble cells have stood backstage in the wonderful theatre that is the brain.Now, though, it seems that they are in fact the real stars of the show.