Neuroplasticity

by Moheb Costandi

Reward, Motivation, and Addiction Addictive narcotic and prescription drugs act on and modify brain systems involved in reward and motivation. The most important of these systems is the mesolimbic pathway, which begins in a small region of the midbrain called the ventral tegmentum. In the human brain, the ventral tegmentum contains approximately 400,000 neurons. These cells synthesize and release the neurotransmitter dopamine and project their long axonal fibers to the nucleus accumbens, part of a set of subcortical structures called the basal ganglia, which are involved in procedural learning, habit formation, and the control of voluntary movement. The nucleus accumbens in turn projects to numerous other brain regions, including parts of the cerebral cortex involved in memory and decision making and the amygdala, a small, almond-shaped structure involved in fear, anxiety, and assigning emotions to our experiences. Normally, these structures cooperate to translate motivation into goal-directed actions in order to obtain natural rewards such as food, water, and sex. The nucleus accumbens plays a central role in these processes. Everything that we find pleasurable causes ventral tegmentum neurons to fire and release dopamine into the nucleus accumbens, which then evaluates how rewarding it is, according to the amount of dopamine released. For this reason the nucleus accumbens is popularly referred to as the brain’s “reward center,” and dopamine as “the pleasure molecule,” al...

Nicotine increases the firing rate of dopamine-producing ventral tegmentum neurons by acting on nicotinic receptors expressed on their surface; opioids, cannabinoids, and benzodiazepines increase their firing rate indirectly, by inhibiting the activity of GABA-producing interneurons in the ventral tegmentum; and psychostimulants such as cocaine, amphetamines, and ecstasy block the dopamine transporter, a membrane protein that normally reabsorbs dopamine once it has been released by neurons into the synaptic cleft.

Pups that are repeatedly licked and groomed during the first week of life are better able to cope with stress and fearful situations in adulthood, compared to those that had little or no contact with their mothers. These differences are associated with alterations in activity of the glucocorticoid receptor gene in the hippocampus. The glucocorticoid receptor plays a critical role in the stress response, and the pups that received high levels of care from their mothers expressed it at higher levels than those who received less attention. These effects were attributable to epigenetic modifications to the DNA, which alter gene expression by changing the physical structure of the chromosomal region containing the genes. Frequent licking and grooming led to epigenetic changes that opened up the chromosomal region containing the glucocorticoid receptor gene and made it more accessible to the cell’s protein synthesis machinery, whereas lack of maternal care caused different epigenetic modifications that closed off the chromosome and reduced gene activity.

A follow-up study by the same researchers suggests that these findings translate to humans. They performed postmortem examinations of the brains of child abuse victims who had committed suicide as adults, and compared them to the brains of suicide victims who had not been abused as children and to those who had died of other causes. They found that the hippocampi of suicide victims who were abused as children had significantly lower levels of glucocorticoid receptor messenger RNA than those of the other two groups.

This work shows that in general, socioeconomic status is associated with variations in the makeup and function of certain brain structures. Children from poorer backgrounds have smaller gray matter volume in the hippocampus, for example, and also exhibit differences in amygdala and prefrontal cortex activity, in comparison to those who are better off. These characteristics are associated with impairments in such domains as attention, memory, and emotional regulation.

mental stimulation and loving relationships are essential for proper brain development, and it immediately suggests multiple interventions that could break the vicious cycle of poverty, reversing or at least minimizing the consequences of childhood neglect or abuse.

But it is very difficult to test whether the epigenetic modifications associated with early life stress are also reversible in humans, and many researchers are focusing instead on what makes some people more resilient than others to the effects of stress and early life adversity.

By contrast, the volume of other brain regions, in the orbitofrontal cortex, cingulate gyrus, and insula, are seen to decrease. These changes are believed to be linked to changes in the father’s behavior and attitude, making the attachment rewarding and strengthening the bond between father and child;

Cajal’s own views about the brain’s capacity for plasticity are, however, ambiguous, and in fact he followed this famously pessimistic statement by remarking that “it is for the science of the future to change, if possible, this harsh decree.”

neurotransmitter release regulates the number of myelin sheaths formed by individual oligodendrocytes, and that oligodendrocytes preferentially wrap newly formed myelin around electrically active axons, suggesting that myelin can be redistributed in an activity-dependent manner.

Short-term changes in myelin distribution could affect the extent of synchronicity between distant brain regions—a property that is increasingly regarded as an important aspect of information processing.

Research published in the past few years, however, shows that neuronal identity can change, too. It’s thought that most neurons synthesize and release just one neurochemical transmitter, and so they can be classified as “dopaminergic,” “GABAergic,” or “glutamatergic,” according to which one they use. But it is now clear that at least some neurons can use more than one transmitter and, more surprisingly, that mature neurons can switch the transmitter they use, converting their excitatory synapses into inhibitory ones, or vice versa.

Neurons can also be classified according to their electrical properties. For example, basket cells, the interneurons that control closure of the critical period in the visual cortex, are believed to exist in as many as 20 different types, the best known being the “fast-spiking” and “slow-spiking” ones, characterized according to the time frames of their responses. But it turns out that these cells can switch back and forth between fast- and slow-spiking activity, in response to neuronal activity. They appear to be constantly tuned in to neuronal network activity, and to change their firing properties in response by means of a protein that enters the nucleus and regulates the expression of potassium channels, which determine the cell’s firing rate. This suggests that the 20 apparently different types basket cells are actually one and the same, and that they morph along a continuum in an activity-dependent manner. Basket cells form networks that modulate neuronal network activity, and so this identity-switching mechanism could significantly impact neuronal population dynamics by altering the ratio of fast- to slow-spiking cells within a given network of neurons.

Ultimately, neuroscientists hope to bridge the chasm between molecular events and behaviors and thought processes, and to understand how they relate to one another. The brain is increasingly viewed as one vast network containing several hundred richly interconnected “hubs,” and huge amounts of money and effort are now being spent mapping brain connectivity at multiple scales. At smaller scales, brain connectivity appears to be constantly changing, but at larger scales it appears much more stable.

individual brains may differ in their capacity for plastic changes, so that the same experiences could induce different extents of neuroplasticity, and different types of plastic changes, in different people.

It’s very likely that no two brains are alike and, therefore, that there is no such thing as a “textbook brain.” Your brain is, to a large extent, unique, custom-built from the life experiences you have had since being in your mother’s womb, to meet the demands you place on it today. Neuroplasticity therefore lies at the heart of what makes us human, and of what makes each of us different from everyone else.