House of Mind

Coming from a lab focused on mother-pup interactions and attachment during infancy, I never really considered the contribution of paternal care to offspring survival and development. Needless to say, I myself am guilty of minimizing the role and contribution of paternal behavior on offspring development. Much to my (pleasant) surprise, I found that there is much relevant work being done in this underrepresented area of neuroscience.

So why is the study of paternal care and related behaviors important? Let’s start off by pointing out that, much like maternal care, paternal behaviors strongly influence the emotional and social development of their offspring as well as increasing survival rate. In addition, think about this: in human culture, who is more likely to leave a household? Fathers leave the family nucleus more frequently than mothers and they are also more likely to become abusive. It should then be no surprise that the children of these fathers grow up under stressful conditions and have a higher susceptibility for developing abnormal psychosocial outcomes. In order to gain insight into the neural substrates and circuits underlying paternal behaviors, scientists are employing a vast number of animal models (i.e. birds, fish, marmosets, hamsters, voles, mice) and studying different elements of paternal care behaviors. Although the use of model organisms to study complex interactions (that are in turn influenced by society and culture), such as those pertaining to human paternal care that encompass more abstract behaviors like planning, provisioning through financial means and perceptual warmth, they provide important clues into the different mechanisms and operating factors related to the spectrum of paternal behaviors.

Examples of Paternal Behaviors in Model Animals:

• Grooming
• Thermoregulatory behaviors (crouching, huddling to provide warmth)
• Pup retrieval
• Nest building
• Food gathering
• Baby-sitting/guarding (aka protection)

Factors modulating paternal involvement/care:

1. Environment: Some species that are not usually paternal will become so when faced with tough environmental conditions (i.e. facultative care). The role of photoperiod is also known to influence bheavior of the non-parental male in some species. For example, the meadow vole will begin biparental care during the colder months of the year when there is also less daylight hours.
2. Prior Experience: Previous pup experiences may affect future paternal behavior. For example, repeated pup exposure is able to induce paternal behavior in virgin male rats (FYI: pup experience is able to induce maternal behavior in virgin female rats as well.
3. Maternal variables: Females are also affected by some of the same factors influencing paternal care, and they can in turn modulate/regulate paternal behavior. For example, brief cohabitation with a female is able to decrease the latency of paternal behavior initiation in prairie voles. Also, mother monkeys sometimes direct threat vocalization towards the fathers when these initiate contact with infants, thus limiting their parental involvement.

The role of paternal involvement in offspring development has also gained recent popularity due to studies that have raised the possibility that epigenetic mechanisms in fathers may contribute to the transgenerational transmission of stress-induced psychopathologies. For example, major depressive disorder (MDD) is a highly heritable psychiatric disorder that is influenced by exposure to many forms of chronic stress. Moreover, stress has been suggested to contribute to MDD via epigenetic alterations that may be passed on to subsequent generations, thus increasing vulnerability to MDD. 

A recent reserach study led by Eric Nestler at Mount Sinai School of Medicine employed a chronic social defeat stress paradigm in adult male mice to investigate the transgenerational transmission of stress-vulnerability. The group, who had previously demonstrated that chronic social defeat stress induces depression and anxiety-like behaviors, studied whether exposure to chronic social defeat stress causes stress-related abnormalities in the F1 (first generation) offspring of the stressed fathers. Also, they examined known biomarkers of depression (i.e. corticosterone vascular endothelial growth factor) in male and female offspring of stressed fathers. The group found that male mice bred from defeated fathers showed a robust behavioral phenotype characterized by pronounced social and neurobehavioral deficits in multiple anxiety and depression related behavioral tasks (elevated plus maze, novelty exposure, forced swim test). However, this effect was limited in females and not as robust. The male offspring of defeated fathers also showed higher levels of corticosterone and lower levels of VEGF.

In order to directly determine a role for epigenetics,  the group also did something very clever and used in vitro fertilization (IVF)  in addition to regular breeding. However, they failed to find marked neurobehavioral abnormalities in these IVF offspring, suggesting that the transgenerationally transmitted behavioral phenotypes likely occur through behavioral mechanisms, although a small role for epigenetics is apparent.

Sources:

Kentner, Abizaid, Bielajew. 2010.  Modeling Dad: Animal Models of Paternal Behavior. Neuroscience and Biobehavioral Reviews. 34 (3): 438-451.

Dietz et al. 2011. Paternal transmission of stress-induced pathologies. Biological Psychiatry. 70 (5): 408-414.

Dietz and Nestler. 2011. From father to offspring: paternal transmission of depressive-like behaviors. Neuropsychopharmacology. 37 (1): 111-2.

Although city life offers many advantages and even some health benefits, meta-analyses indicate that city living is a substantial risk factor for mood and anxiety disorders. Basically, people who live in cities have a higher incidence for these disorders. Also, genetically predisposed individuals are at an even greater risk if they are brought up in cities. In schizophrenia, for example, the incidence is nearly doubled in subjects that were born, raised and currently lived in the city. And let’s not forget that, usually, with city life comes a more stressful social environment, a factor known to exacerbate many psychiatric disorders, particularly the ones mentioned above. 

So how is it that being from/living in a certain place can affect how your brain works? 

In order to understand this question, Lederborgen et al (2011) used functional magnetic resonance imaging (fMRI) to study the neural responses of subjects taking a social stressor task that consisted of solving math problems under time pressure while also receiving negative feedback from the experimenter. The subjects differed in terms of their living conditions, as they were from urban (+100,000 people), town (+10,000) or rural areas.

The task was an effective stressor as it successfully induced stress, indexed by increases in heart rate, blood pressure, and salivary cortisol (stress hormone) levels. In addition, there was significant activity in brain areas implicated in the stress response, emotion, and social behavior. Of these, 2 major areas exhibited the most robust changes: 

• Amygdala: Current city living was associated with increased amygdala activity. Activation positively correlated with the size of the city that the individual currently lived in, with city dwellers having the highest levels of amygdala activation.
• Anterior cingulate cortex: Activation correlated with the upbringing (or how long) a person had lived in a city. Individuals that were entirely brought up in cities showed the greatest perigenual anterior cingulate cortex (pACC) activation. This region is important due to its role in the regulation of amygdala activity during negative affect and stress. 

Moreover, the authors show evidence suggesting that there is reduced functional connectivity between the amygdala and specifically, the perigenual anterior cingulate cortex of those participants that were born and raised in cities. Considering that weakened coupling of these areas has also been linked to genetic risk for psychiatric disorders, these findings have important clinical relevance. Now let’s stretch our thinking- with urbanization increasingly becoming the way of life and the very real risk of overcrowding, what does this mean for brain development?

The authors state that the results were not explained by demographic/clinical factors or a number of other variables. They have also been able to replicate their findings in a larger and better distributed sample. However, they recognize that limitations of their work include that their study was purely correlational and they discuss the need for a larger scale study that has ways of identifying and measuring more variables that may be related to city living. 

For those of you that live (or were brought up) in cities, cheer up. There are a variety of reasons for choosing to live (and enjoy) the city life. In a way, the city has its way of forcing you into developing coping strategies- which is a good thing, right? Now here’s something to think about: psychologists have even found that one of the factors accounting for the preference of city living is the degree of control that people have (and feel they have) over their lives. 

Sources: 

Kennedy, DP & Adolphs R. 2011. Stress and the city. Comment on: Nature. 474: 452-3. doi: 10.1038/474452a

Lederborgen et al. 2011. City living and urban upbringing affect neural social stress processing in humans. Nature. 474: 498-500. oi: 10.1038/nature10190

Most of you have probably heard that working out not only makes you feel better but also gives your brain power a boost. But is this really true? And if so, how is exercise related to enhanced mood or cognitive abilities/performance?

So…. Everyone knows that living a sedentary lifestyle is not the way to go. In fact, a sedentary lifestyle brings about a wide array of negative consequences; one of them being increased risk for cardiovascular and metabolic diseases. However, exercise has been determined to serve as a protective factor that can reduce the incidence of cancer, heart disease, and even diabetes. 

Van Praag wrote a review in which she revised many of the known benefits of exercise. Take a look:

• Enhancement in cognition
• Counteracts age-related memory decline
• Delays the onset of neurodegenerative diseases
• Aids in recovery after brain injury
• Helps in recovery from depression 

I suppose you’re wondering: but, how?!

Thus far, the current notion on the mechanism by which all these benefits occurs is via increased and robust neurogenesis (or neuronal birth) in the hippocampus. If you’d like to learn a bit more about neurogenesis, click here for an older post on that topic. Physiologically, exercise not only increases the number of neuronal proliferation, but also the number of spines and dendrites (remember that this is where messages from other neurons arrive to!). 

Adult neurogenesis is dependent/can interact with many factors including:

• Stress
• Aging
• Environmental Enrichment
• Physical Activity

As you would probably assume, stress and aging are associated with decreased adult neurogenesis while enriched environments and exercise are associated with increased neurogenesis. Moreover, exercise-induced neurogenesis has been linked to enhanced hippocampal synaptic plasticity, as modeled by long-term potentiation (a physiological model of learning and memory) studies from different labs. Additionally, changes in synaptic plasticity have been observed to occur in the same regions in which neurogenesis was stimulated through exercise! 

Sources:

This is the main review I used for this post. It’s a great resource because it talks about neurogenesis and exercise as well as the relationship with cognition (and other diseases like Huntington’s, Alzheimer’s, etc…) 

van Praag, Henriette. 2008. Neurogenesis and Exercise: Past and Future Directions. Neuromolecular Medicine. 10: 128-140. DOI 10.1007/s12017-008-8028-z 

Take home messages: 

• Corticotropin releasing factor (CRF) acts in the ventral tegmental area (VTA), a primary source of dopaminergic neurons and an integral part of the mesolimbic reward pathway, to regulate dopamine (DA) neurotransmission. 
• A large reward (large reward magnitude)  will enhance motivated behavior. 
• A large reward magnitude also enhances DA release in response to cues and rewards.
• CRF, a hormone and neurotransmitter implicated in the stress response (HPA axis), in the VTA will attenuate motivated behavior in a dose-dependent manner and this effect is not due to motor suppression. 
• CRF in the VTA attenuates phasic DA release (burst DA release as opposed to a more gradual release) specifically to rewards, not the cues related to the rewards. 
• Satiety (being full) will reduce motivated behavior (in this case the reward was food pellets) as well as DA release to rewards (but not cues). 

Author Abstract (Phillips, et. al) : Phasic dopamine release during reward and effort manipulations: Effects of corticotropin release factor. 

The effort an individual is willing to exert to obtain a reward is dependent upon one’s motivational state as well as the value of the reward. Contemporary theories of dopamine function suggest that dopamine release, particularly in the striatum, is involved with enabling high-effort behaviors. Motivated behaviors can be influenced by stressful stimuli and stress-released neuropeptides such as corticotropin-releasing factor (CRF). The behavioral effects of stress on motivation could involve the midbrain dopamine system as (i) stress increases dopamine levels, (ii) CRF is released into the midbrain during stress, and (iii) CRF increases the firing rate and potentiates glutamate receptor current in dopamine neurons. Thus, we hypothesized that CRF in the VTA will elevate phasic dopamine release and increase the effort exerted to obtain a reward. However, before addressing this pharmacological question it was important to first determine how natural manipulations of motivational state and reward magnitude influence phasic dopamine release during high-effort behaviors.

We utilized fast-scan cyclic voltammetry to examine phasic striatal dopamine release to rewards and reward-predictive cues in rats performing an operant task under a progressive ratio (PR) reinforcement schedule for natural reinforcers. In separate sessions, we assessed behavior and dopamine release in rats under different motivational states (food-deprived or free-fed) or working for rewards of different magnitudes. The cumulative number of rewards earned scaled with the reward size in a given PR session. Interestingly, we found that motivational state and reward size robustly scaled reward-evoked dopamine release, while cue-evoked dopamine release was less sensitive to these manipulations. After establishing the effect of natural manipulations, we next examined how CRF injections into the midbrain affected behavior and dopamine release during PR sessions. Contrary to our hypothesis, CRF injected into the midbrain lowered the breakpoint in PR sessions. Furthermore, CRF injections attenuated reward-evoked dopamine release but did not affect cue-evoked dopamine release. Together, these results suggest that CRF modulates motivated behavior by affecting either dopamine neurons responsive to reward delivery and/or inputs to the midbrain representing the delivery of rewards.