House of Mind

"Biology gives you a brain. Life turns it into a mind" - Jeffrey Eugenides

  • 20th January
    2014
  • 20
The brain is a tissue. It is a complicated, intricately woven tissue, like nothing else we know of in the universe, but it is composed of cells, as any tissue is. They are, to be sure, highly specialized cells, but they function according to the laws that govern any other cells. Their electrical and chemical signals can be detected, recorded and interpreted and their chemicals can be identified; the connections that constitute the brain’s woven feltwork can be mapped. In short, the brain can be studied, just as the kidney can.
David Hubel, The Brain
  • 11th November
    2013
  • 11

Entrainment of circadian rhythms by stressful stimuli: Evidence from a rodent model


Circadian rhythms in humans and animals are sensitive to stressors and changes in the emotional state. However, whether circadian rhythms can be entrained by fear stimuli had not been directly investigated until now. To test this, circadian behaviors of male Long Evan rats maintained on an LD (12-h light/12-h dark) cycle were monitored in a live-in chamber comprised of safe nesting and risky foraging areas. Initially, animals pressed a lever to procure food pellets in the foraging area and were entrained to the environmental conditions for a week. 

Then, animals were subjected to (i) 14 days of ‘Unsignaled’ footshocks (0.8 mA; pseudo-random 2 shocks/hr) which were delivered only during the dark phase of the LD cycle, and (ii) 14 days of ‘Signaled’ footshocks (a 9-sec light cue preceding the footshock) also during the dark cycle (counterbalanced orders). During the unsignaled footshock, rats reversed their normal circadian feeding behavior, meaning that they exhibited more feeding behavior during the light phase than the dark phase, and showed arrhythmic locomotor activity. During the signaled footshock, however, rats returned to or conserved their normal circadian feeding (i.e., the feeding behavior was observed mostly during the dark phase) and rhythmic locomotor activity. In sum, rats exposed the unpredictable stressor (i.e. unsignaled shock) quickly learned to adapt their behavior by shifting their meal time earlier so that there was a lesser possibility of the feeding coinciding with the shock. Furthermore, lesioning the amygdala in these animals prevented the reversal of the feeding time, suggesting that amygdala function is causal in producing this effect and postulating a new role for amygdala function. 

These results suggest that amygdala-dependent fear, associated with environmental threats limited to the naturally active phase (i.e. dark), can act as a non-photic entraining stimulus and lead to circadian activity during the naturally inactive phase (i.e. light). Importantly, there is growing evidence suggesting  a link between mood disorders such as depression and anxiety and disturbances in circadian rhythm, which makes determining the mechanism underlying the entrainment of circadian rhythm by fearful or stressful stimuli of clinical relevance. Moreover, if aversive conditioning is able to induce changes in circadian rhythm, can appetitive conditioning do the same? 

Source: 

E.E. S. Kim, J. Kashima, O. Motch, H.O. de la Iglesia, J.J. Kim. Entrainment of circadian rhythms by fear. Program No. 189.04/HHH29.2013. Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2013. 

 

  • 10th November
    2013
  • 10

Sires compensate for dam’s poor maternal behavior

Paternal care is typically studied in monogamous and biparental rodents, such as prairie voles, and marmosets in the wild, where the sires are spontaneously paternal. In other rodent species, paternal behaviors are induced by environmental factors such as sensory input from dams or pups. Importantly, the putative neural systems in these type of species are different from those of biparental species. Koh and Kim conducted a study in which they observed that wild type (WT) sires become significantly more attentive when they are paired with PLCb1-KO dams, which neglect pups for around 18 hours postpartum. For example, WT sires mated with KO dams showed more active parental behaviors including nesting, grooming, licking and hovering over the pups. Moreover, they were faster at retrieving pups in the 3 pup retrieval task. Importantly, the company of this paternally more attentive sire fundamentally affected pup survival rate (i.e. pups were more likely to survive even if the dam was neglecting them). In addition, the group assessed FosB expression ( amarker of neural activity) in these paternally responsive sires and found that “good dads” had increased expression in the core of the nucleus accumbens (critical part of the reward circuit) and decreased expression in the caudate putamen and central nucleus of the amygdala. 

These results confirm the notion that paternal attentiveness may be modulated dyanmically by environmental factors (i.e. maternal phenotype of the dam and/or resultant condition of the pups). Furthermore, this type of modulation may be of evolutionary adaptive value, as the sire is increasing the probability that his genes will survive and potentially reproduce later on.  

Source:

H.Y. Koh and H. Kim. Paternal attentiveness can be affected by behavioral phenotype of the dam. Program No. 174.18/VV6.2013. Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2013. Online.  

  • 10th November
    2013
  • 10

Rodent model suggests that prenatal music appears to be beneficial for dams but detrimental for their offspring

Music has overarching influence in human life. For example, music is capable of inducing physiological responses such as as reducing anxiety and attenuating depression. Furthermore, music is thought to promote fetal development and human fetuses near the last trimester are known to respond to music with heart rate acceleration and motor responses (Kisilevsky, 2004; Al-Qahtani, 2005), since the prenatal period is characterized by its high sensitivity to environmental situations. Recently, there has been an increase in the amount of women who play music for their babies in utero, and images of a women wearing headphones around their pregnant bellies have become more common (just google pregnant women listening to music if you don’t believe me). However, the effects of playing antenatal music in humans are controversial and evidence from controlled longitudinal studies is lacking… 

To shed some light on this issue, Kubota and colleagues investigated the effects of prenatal music on maternal behavior and offspring behavior in rodents. In short, pregnant rats were exposed to 1 hour of Mozart (65dB) a day during the dark period while they were during the late gestational stage while control dams were exposed to a similar decibel ambient noise. The researchers found that music exposure increased the frequency of positive maternal behaviors following childbirth, as pregnant dams exposed to music during the late gestational period showed increased licking and grooming of their pups and decreased time spent away from their pups during the early neonatal period (PN3-6) compared to control mothers not exposed to music. Notably, this result is consistent with human studies suggesting that pregnant mothers who played music for or sing lullabies to their babies in utero report increased feelings of relaxation and attachment to their infant.

However, Kubota and colleagues found that although prenatal music exposure did not affect anxiety related behavior in the offspring, animals exposed to prenatal music showed increased depressive-like behavior in the Forced Swim Test 6 weeks after birth (i.e. PN45- adolescence), as indexed by increased time spent immobile as well as reduced swimming and climbing. Considering that the group assessed maternal behavior during the neonatal period and found enhanced maternal care in dams previously exposed to music, it seems unlikely that this adverse behavioral phenotype comes as a result of variations in maternal care. I’m not sure if this study will expand (and maybe assess neural correlates of this behavior) and become a publication, but it certainly makes you think twice about the effects of prenatal music and child development. 

Anybody know of similar (i.e. longitudinal) studies done on human infants? 

Sources: 

Al-Qahtani (2005). Foetal response to music and voice. Aust N Z J Obstet Gynaecol. 45(5):414-7.

Kisilevsky, et. al. (2004). Maturation of fetal responses to music. Dev Sci. 7(5):550-9.

N. Kubota, Y. Takano, S. Yanagita, T. Matsuzawa, K. Takeda. The effects of prenatal music on maternal behavior and offspring behavior. Program No. 174.16/VV4-DP7.2013. Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2013. Online. 

  • 9th November
    2013
  • 09

A rodent model of teenage bullying

Many teenagers experience bullying, and adolescent bullying is a severe stressor associated with greater incidence for psychiatric disorders that can persist into adulthood, including depression and substance use disorders. Such disorders are characterized by deficits in executive functioning, which are known to be mediated by medial prefrontal cortex (mPFC) and dopamine (DA) activity. 

In order to assess how bullying changes DA in the mPFC after adolescent bullying, MJ Watt and colleagues employed a rodent model of repeated social aggression during adolescence in which peripubertal rats were exposed to an older and aggressive adult male for 10 minutes a day over a 5 day period (PN35-39). Following each “bullying bout”,  a wire mesh was placed in the chamber to separate the intruder (i.e. aggressor) from the test rat for 25 minutes, which is a form of chronic psychosocial stress and may serve to model the intimidation many teens may experience with their own aggressors (i.e. school mates, peers, etc). The researchers found that rats experiencing adolescent social defeat show increased mPFC DA activity at PN40 (the day after the last bullying session), which was maintained until PN49- even after the stressor hadn’t been experienced since PN39. However, at PN56 these same animals had decreased mPFC DA activity, which may be due to over-compensation to reduce the elevated activity seen from PN40-49. Furthermore, mPFC DA hypofunction induced by social defeat stress was specific to animals experiencing it during adolescence, as the same manipulation in adults only led to increased mPFC DA activity following exposure to social aggression. Importantly, this manipulation did not change norepinephrine (NE) or serotonin (5-HT) activity in the mPFC, and animals experiencing social defeat stress during adolescence did not become more aggressive later in development. Collectively, these findings suggest that mPFC DA is particularly susceptible to social stressors during adolescence and that social defeat changes not only mPFC DA function, but also behavioral responses to later life social events.

On a side note, I would be interested to see how these animals perform in  a go/no-go task or in a rodent model of the Iowa gambling task. Also, how would these animals perform in a self-administration paradigm and how would it be modulated by social context? Also, I really like the idea of framing  the social defeat paradigm as a model of bullying instead of depression. Kudos!

Lesson of the day: Be nice to each other, because you never know how your words/actions are affecting the other person. 

Source: 

M.J. Watt, L.C. Miller, J.L Scholl, K.J. Renner, A.M. Novick, G.L. Forster. Trajectory of alterations to cortical dopamine activity in a model of teenage bullying. Program No. 84.03/ZZ23.2013. Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2013. Online. 

  • 24th October
    2013
  • 24