Know your brain: Olfactory bulb

Where is the olfactory bulb?

The olfactory bulb is a structure found on the inferior (bottom) side of the cerebral hemispheres, located near the front of the brain. There is an olfactory bulb at this location in both cerebral hemispheres. The olfactory bulb is attached to the cerebral hemisphere by a long stalk often referred to as either the olfactory stalk or olfactory peduncle.

What is the olfactory bulb and what does it do?

The olfactory bulb is an essential structure in the olfactory system (the system devoted to the sense of smell). Olfaction begins when odorant molecules enter the nasal cavity through inhalation or by rising from the mouth (e.g. during the chewing of food). Those molecules interact with olfactory receptors, which are part of a family of G-protein coupled receptors. Stimulation of these receptors causes the production of second messengers like cyclic AMP (cAMP), which leads to the opening of ion channels and the generation of action potentials in olfactory receptor cells.

The axons of these olfactory receptor cells terminate in the olfactory bulb, where they converge on the dendrites of olfactory bulb neurons in small clusters called glomeruli (plural for glomerulus, which is a term sometimes used in anatomy to refer to a small cluster of structures). Each glomerulus consists of the axons of several thousand olfactory receptor neurons converging on the dendrites of a small collection (~40 to 50) of olfactory bulb neurons, and each glomerulus only receives input from one type of odorant receptor. This does not mean that each glomerulus is only capable of detecting one odor, as each type of odorant receptor is capable of detecting multiple odorants. The olfactory bulb is patterned in such a way, however, that similar odorants often stimulate glomeruli found close to one another in the olfactory bulb. This creates an organization in the olfactory bulb that seems to be related to odorant structure.

There are several types of neurons in the olfactory bulb. These include mitral cells, tufted relay neurons, granule cells, and periglomerular neurons. The mitral cells and tufted relay neurons form connections with olfactory receptor neurons in the glomeruli. They receive olfactory information and then carry it from the olfactory bulb to the olfactory cortex, the main site for the processing of olfactory information. The olfactory cortex consists of several cortical areas that receive information from the olfactory bulb, including the piriform cortex, entorhinal cortex, an area of cortex covering the amygdala known as the periamygdaloid cortex, and two regions known as the olfactory tubercle and anterior olfactory nucleus, respectively. Granule cells and periglomerular neurons are both interneurons that are thought to be involved with fine-tuning the processing of olfactory information by doing things like helping to sharpen the contrast between different odorants.

The olfactory bulb tends to be much smaller in humans and other primates than in animals that rely more heavily on a sense of smell to provide them with information about their environment (e.g. rodents, dogs, etc.). Assertions that the human sense of smell is "underdeveloped" due to lack of importance may be overblown, however. Studies suggest humans may be able to detect up to a trillion different odors and that we are capable of using olfaction much more extensively when asked to complete a task that relies heavily on olfaction. Also, those who intentionally test their olfactory system regularly (e.g. wine tasters) are able to demonstrate vastly refined olfactory perception. Humans have even been found to be able to utilize the same type of scent tracking used by animals like bloodhounds. Thus, it may be that we have the capacity for greater olfactory discrimination but not a pressing need to refine these skills except in certain circumstances.

The olfactory bulb is also a brain region of interest because it is one of the few places in the brain where new neurons appear over the course of the lifespan. This phenomenon has mostly been observed in rodents, however, and there is some debate about its prevalence and/or importance in humans. In rodents, the new neurons that are added to the olfactory bulb are primarily produced in an area known as the ventricular zone, which lines the walls of the lateral ventricles. The new neurons then migrate to the olfactory bulb, where they differentiate into specific functional cell types. Estimates are that thousands of new olfactory bulb neurons are produced every day in the rodent brain. The reasons for this prolific neurogenesis in the olfactory bulb are not clear, although it has been proposed that it is an important component of synaptic plasticity in the structure and that it might help the olfactory bulb to adapt to the frequently changing composition of olfactory receptor neurons, which only have about a 60 day lifespan in rodents.

References (in addition to linked text above):

Kandel ER, Schwartz JH, Jessell TM 2000. Principles of Neural Science, 5th ed. McGraw-Hill, New York.

2-Minute Neuroscience: Periaqueductal gray

The periaqueductal gray, or PAG, is an area of gray matter that surrounds the cerebral aqueduct in the brainstem. Although it is associated with a number of functions, it is best known for its role in analgesia, or pain reduction. In this video, I discuss the PAG and the pathway by which it is thought to be able to inhibit pain signals from the spinal cord.

Know your brain: Mirror neurons

Where are mirror neurons?

Image from: Gross L. Evolution of neonatal imitation. PLoS Biol. 2006 Sep;4(9):e311. doi: 10.1371/journal.pbio.0040311

Mirror neurons were first identified in the premotor cortex of monkeys in 1992, and since that time they have also been found in several other areas of the monkey brain, including the primary motor cortex, inferior parietal lobulefrontal cortex, and the area surrounding a sulcus called the intraparietal sulcus.

There is very little conclusive evidence that mirror neurons exist in the human brain, although there is evidence from neuroimaging studies that indicates there are neurons in the human brain that display patterns of activity similar to the mirror neurons identified in the monkey brain. There is, however, one study to date that directly recorded the activity of purported mirror neurons in the brains of human patients who were being prepared for neurosurgery. Although this study could only explore certain areas of the brain (which didn't include the regions most frequently associated with mirror neurons in monkeys), investigators found neurons in the supplementary motor area and temporal lobe that displayed properties of mirror neurons. This, combined with the neuroimaging data mentioned above, suggests that mirror neurons likely exist in the human brain as well as the monkey brain.

What are mirror neurons and what do they do?

In 1992, a group of researchers at the University of Parma in Italy were recording the activity of individual neurons in the brain of a macaque monkey. They were observing neurons in the premotor cortex---specifically a region of the premotor cortex called area F5. Previous research had found neurons in this area to be active during goal-directed hand movements (e.g. grasping, holding, etc.). The investigators at the University of Parma were attempting to further understand this type of neural activation when they observed something surprising.

They noticed that neurons in the F5 region of the monkey's brain were activated not only when the monkey moved its hands, but also when the monkey observed an experimenter using his or her hands (e.g. to pick up a food reward and place it in the testing area). Four years later, they named these neurons mirror neurons because they seemed to be active not only when monkeys performed a particular action, but also when they saw someone else perform a similar action.

As mentioned above, since their initial discovery mirror neurons have been found in various other regions of the monkey brain (as well as in the brains of other species like songbirds), and there is evidence to suggest that mirror neurons exist in human brains. 

The discovery of mirror neurons has generated a type of excitement both in and outside of the scientific community that is not often seen in response to scientific findings. Some have interpreted the activity of mirror neurons as the basis for our ability to understand the actions of others---a deduction thought by some to be unjustified, and one that has led to other (perhaps even less justifiable) extrapolations. For example, some have claimed that mirror neurons provide the necessary neural machinery for empathy, complex social interactions, language---and even that they are responsible for the rapid cultural advancement of the human race that led to us becoming modern humans.

Based on these proposed roles for mirror neurons, researchers began to speculate that impaired functioning of mirror neurons may be the basis for certain psychiatric disorders. For example, some have argued that dysfunctional mirror neurons underlie autism spectrum disorders (ASD). This hypothesis, sometimes called the "broken mirror hypothesis," suggests that individuals with ASD have abnormalities in mirror neuron networks that cause them to have an impaired ability to experience empathy, difficulty understanding the actions of others, and deficits in various aspects of social interaction ranging from eye contact to language. 

Indeed, in the few decades since their discovery, mirror neurons have been credited or blamed for a long list of things ranging from simple feats like helping us to enjoy watching sports to complex emotions like compassion to disorders like ASD and schizophrenia.

The problem with these claims, however, is that they are mostly unsubstantiated. The first caveat to speculation about mirror neurons is that the vast majority of concrete evidence we have to support the existence of mirror neurons comes from studies in monkeys (concrete evidence in this case refers to evidence obtained from monitoring the activity of individual neurons---something that is difficult to do in humans except in rare circumstances like the example cited above where mirror neurons were explored in patients preparing for neurosurgery). Therefore, at this point we cannot with confidence attribute behaviors to mirror neurons unless we have been able to record mirror neuron activity while monkeys have exhibited such behaviors. Thus, we do not yet have the evidence to consider complex human emotions and behaviors (which can only be roughly approximated in studies of non-human primates) as attributable to mirror neurons. 

Similarly, the evidence to point to dysfunctional mirror neurons as the main causal factor in human psychiatric disorders is lacking. Let's take the hypothesis that dysfunctional mirror neurons contribute to ASD as an example. This hypothesis was initially supported by two highly-cited studies from the early 2000s. One was a neuroimaging study that found reduced activity in autistic patients in a part of the brain thought to be heavily populated with mirror neurons. The other used electroencephalography to measure electrical activity believed to be indicative of mirror neurons; again, individuals with ASD appeared to display abnormalities in this activity.

Each of these studies, however, failed to replicate multiple times. Additionally, critics of the "broken mirror hypothesis" have been quick to point out that there is not good evidence that individuals with ASD even have deficits in understanding the intentions of others. Thus, the "broken mirror hypothesis" has been found to be wanting, and other hypotheses that attribute psychiatric abnormalities to mirror neurons are similarly in need of more support to make them tenable.

Even when it comes to just the basics of mirror neuron function, we are still searching for answers. For example, some researchers argue that the evidence that mirror neurons are involved with something as abstract as understanding actions is inadequate. According to this perspective, even if mirror neurons may be involved with functions like recognizing basic movements, selecting movements to make, etc., the evidence isn't conclusive to suggest mirror neurons are involved with a type of higher-level cognition like understanding the behavior of others. This is a critically important point as the idea that mirror neurons help us to understand others' actions is essential to the interpretation of mirror neurons as being involved in behaviors like empathy and social interaction---and indeed is the basis for much of the enthusiasm about mirror neurons in general.

Thus, while mirror neurons have been lauded for their ability to explain a variety of uniquely-human behaviors and accomplishments, it seems that we may have jumped the gun a bit on our interpretation of the activity of these cells. Much more research still needs to be done before we can say with confidence what mirror neuron activation really means in terms of behavior---and indeed before we can be sure that mirror neurons are as prevalent in the human brain as they are in the monkey brain. As with all scientific discoveries, it is best to be conservative in our interpretations until they are the only logical ones to make based on the data.

References (in addition to linked text above):

Hickok G. Eight problems for the mirror neuron theory of action understanding in monkeys and humans. J Cogn Neurosci. 2009 Jul;21(7):1229-43. doi: 10.1162/jocn.2009.21189.

Kilner JM, Lemon RN. What we know currently about mirror neurons. Curr Biol. 2013 Dec 2;23(23):R1057-62. doi: 10.1016/j.cub.2013.10.051.

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Benzodiazepines are a class of drugs commonly used to treat anxiety disorders and sleep disorders. They are thought to exert their effects in the brain by acting at receptors for the neurotransmitter gamma-aminobutyric acid, or GABA. In this video, I cover the the mechanism of action for benzodiazepines and discuss how it is thought to lead to calming effects.