Science


My major research objective is to understand how we learn and how memories are thereafter maintained in the mammalian brain. To do that, we have relied on two general approaches. The first one involves neurogenesis, which is the production of new neurons in the mammalian brain. For many years, indeed decades, we thought that the brain did not make new neurons after birth. In the past several years, it has become accepted that the adult brain, including the human brain, does produce new neurons — and lots of them. As many as ten thousand new neurons are made each day. The discovery (or more accurately, the “rediscovery”) of neurogenesis in the adult has generated a great deal of excitement in the field, because it indicates that we have a great capacity for change and renewal throughout our lifetimes.

NEUROGENESIS AND LEARNING:

The vast majority of new neurons are produced in the hippocampus, a brain region which is critical for select types of learning processes.  However, most of these new cells die within a few weeks. Given that so many cells are born in the hippocampus, we hypothesized that they may be related to the formation of new memories.  Indeed, these new cells can be rescued from death by learning.  That is, when animals are trained to learn something new just as the cells are about to die, the cells do not die.  Rather, the cells survive to become mature functioning neurons.  Not all types of learning keep the new cells alive.  The training task must be relatively difficult to learn and the animal must exhibit some effort as well as develop expertise during training.  Importantly, we do not find that smart animals produce more new cells, but rather smart animals retain more of the new cells as a function of their demonstrated learning. These findings are consistent with the phrase “use it or lose it.”

 

In other studies, we have found that the depletion of new neurons is associated with select types of learning deficits. For example, in the near absence of neurogenesis, animals have great difficulty learning to associate events together in time.  Together, our data suggest that these new neurons are affected by new learning and may even be used in the formation of memories themselves.  Minimally, our data indicate that learning over the course of our lives continues to change our brain and maintains new neurons in the circuitry that would have otherwise died.  We are currently examining how these new neurons are used for future learning opportunities and how they interact with naturally occurring brain oscillations to predict learning potential in the future. It is my hope that these lines of research will lead to important discoveries about the neuronal and psychological processes through which we acquire information and translate it into wisdom.

SEX DIFFERENCES IN LEARNING AND THE BRAIN:

Although controversial, most people recognize the fact that males and females can differ in their ability to learn some types of information.  In our laboratory, we observe that females can learn to associate events in time faster than males can.  However, females do not learn well at all if they were previously exposed to a stressful life experience.  In contrast, males tend to learn faster after a stressful event.  These sex differences are organized during early development by the presence of sex hormones and then expressed in adulthood through the presence of sex hormones.  These sex differences in behavior are also dependent on different brain circuits.  For example, the deficit in learning in females after stress depends on a connection between the prefrontal cortex and the amgydala, whereas the enhanced learning in males depends on activity within the bed nucleus of the stria terminalis.  Therefore, these data indicate that males and females can use different brain circuits and by inference engage differing neuronal mechanisms to learn and respond to significant life experience.

          

Women are much more likely to experience stress-related mental illnesses across their lifetime, including depression, anxiety and post-traumatic stress disorders. Women are also much more likely to suffer from one of the most stressful of all life experiences, that of sexual abuse. Thankfully, hope is not lost for females. For example, the experience of motherhood can protect females from some of the detrimental consequences of stressful life experience. While stress tends to suppress learning in virgin females, it does not do so in females that have just given birth. Perhaps more surprisingly, females that have given birth at some time in their lives learn well, even after a stressful life event, and long after the offspring have left their mother’s side.

These observations indicate that motherhood “protects” women from some of the negative consequences of stress over their lifetime. It is my hope that this line of research will enhance the appreciation for sex differences in the brain. Our most recent data present the possibility that sex differences in mental illness may reflect differences in etiology. If true, we should consider alternative treatment strategies and behavioral therapies for woman than we do for men.