Minders for a healthy mind: IGF-1 and astrocytes

Advancement in medicine and healthcare has increased the average life span of people all over the world. This means a majority of the population is going to age, and be susceptible to the diseases and disorders related to aging. Aging is an inevitable physiological change happening over time. Aging of the brain is associated with a reduction in cognition, significantly affecting subject´s ability to live a normal independent life. It also poses an enormous economic burden on aged subjects and their families (1). It is imperative to find an effective therapy for aging associated cognitive impairments.

GFAP-Primary-antibodies-ab4648-2Insulin-like growth factor-1 (IGF-1) is a signaling protein that plays an important role in regulating learning and memory, and age-related diseases. We see a decrease in the levels of IGF-1 in blood circulation, cerebrospinal fluid and brain (hippocampal) tissue in aged rodents. Moreover, the decline in cognition is reversible with IGF-1 supplementation (2).

Most of the work regarding IGF-1 involves investigations in neurons. However, other cells which are responsible for regulating many functions vital for the normal functioning of the brain are largely ignored. Our lab focuses on investigating the effects of astrocyte-derived IGF-1 on learning and memory. Astrocytes are glial cells involved in the release of several key growth factors, neurotransmitters like glutamate, and molecules like ATP, that are responsible for signal transduction processes (3). Thus, astrocytes are not merely a sidekick, but are responsible for maintaining the microenvironment that supports and nurtures neurons. Disruption of astrocyte´s signaling could affect neurons and ultimately cognition. Astrocytes stained using immunocytochemistry can be seen in the figure alongside (from http://www.abcam.com).

My research focuses on investigating the effects of loss of IGF-1 signaling in astrocytes due to aging, and its effects on the release of neurotransmitters, ATP, and ultimately on learning and memory. We also examine what aspects of cognition are regulated by IGF-1 and astrocytes. The findings will help answer some of the important questions about IGF-1 signaling, astrocytes and cognitive decline during aging.

  1. Ortman, B. J. M., Velkoff, V. a., & Hogan, H. (2014). An aging nation: The older population in the United States. Proc. Economics and Statistics Administration, US Department of Commerce (Vol. 1964). Retrieved from https://www.census.gov/prod/2014pubs/p25-1140.pdf
  2. Ashpole, N. M., Sanders, J. E., Hodges, E. L., Yan, H., & Sonntag, W. E. (2015). Growth hormone, insulin-like growth factor-1 and the aging brain. Experimental Gerontology. 68:76-81.
  3. Gibbs, M. E., Hutchinson, D., & Hertz, L. (2008). Astrocytic involvement in learning and memory consolidation. Neuroscience and Biobehavioral Reviews. 32(5):927-44.

 

Disha Prabhu

Department of Biomolecular Sciences

University of Mississippi

Dissecting Short Term Memory

Am not I / A fly like thee? / Or art not thou / A man like me?                                                (from “The Fly” by W. Blake, 1974)

A key goal in neuroscience is understanding and identifying the molecular mechanisms responsible for learning and memory. Learning is defined as a change in an animal’s behavior in response to experience while memory is the persistence of this behavioral change over time.Learning and memory can be viewed from a geneticist’s perspective as biological traits subject to genetic dissection. Humans share many genes and neural mechanisms with the fruit fly, Drosophila, making it a widely used model organism.Figure-1-The-adult-experimental-set-up-The-flies-are-trained-and-tested-in-a-T-maze

Our lab looks at olfactory associative memory formation by training flies to associate an odor with an electric shock (see Figure). Flies are exposed to an odor followed by an electric shock (Figure, A), and then exposed to another odor with no shock (Figure, B). The flies’ memory is tested by letting them choose between two arms in a T-shaped maze, one holds the shock-associated odor and the other the safe odor. If the flies formed a memory about the odors, they will go to the safe arm (1).

Researchers have found they can stop learning by genetically manipulating the expression of certain genes in the Drosophila brain using sophisticated transgenic systems (2). This allows geneticists to have precise control over where and when genes are expressed. We can use transgenic systems to induce Pertussis toxin or PTX which stops learning in flies. PTX inhibits a G-protein called G(o) that is required in memory formation (3). G-proteins are signaling proteins and are highly conserved across species such as Drosophila, bovine, mice, and humans. PTX is regulated by the feeding of doxycycline. Once we stop this feeding, and give the flies some time to recover, we see that they can learn again.

My focus is on neurons within the mushroom body, which has a flexible organization that is similar to that of the mammalian brain. My goal is to further dissect the role of G(o) proteins in these neurons during short term memory, which is responsible for the temporary storage of information. The findings will provide the identification of the subset of neurons within the mushroom body that are involved in memory acquisition during short term memory.

  1. Malik, B. R., and J. J. Hodge. 2014. ‘Drosophila adult olfactory shock learning’, J Vis Exp: e50107.
  2. Roman, G. 2004. ‘The genetics of Drosophila transgenics’, BioEssays, 26: 1243-53.
  3. Ferris, J., G. Hong, L. Liu, and G. Roman. 2006. ‘G(o) signaling is required for Drosophila associative learning’, Nature Neuroscience, 9: 1036-40.

Maria Pena

Department of Biology

University of Mississippi

Stress is not sexy

Males that are unable to effectively compete with other males often find alternative ways to acquire mates (1). Males green treefrogs (Hyla cinerea), for example, will alternate between calling behavior and non-calling satellite mating behavior where they crouch near calling males and attempting to intercept females attracted to the calling male’s vocalizations.

Blog pictureTwo factors have emerged as key variables predicting mating behavior in frogs and toads: 1) vocal attractiveness and 2) the stress hormone, corticosterone (CORT). However, there is little understanding of how both vocal attractiveness and levels of circulating CORT are interrelated and whether these factors are mutually exclusive in governing satellite behavior. My research focused on filling this gap in our knowledge by performing a hormonal manipulation in which I injected calling male Hyla cinerea with CORT and assessed the effects of administration on vocal attractiveness and calling behavior. Firstly, males that were injected with corticosterone exhibited a decreased time spent calling; females prefer males with a high time spent calling (2). Secondly, 92% of the males injected with CORT adopted satellite behavior. Lastly, CORT negatively affected calling behavior independently of changes in testosterone level. This is important because CORT is generally hypothesized to influence reproductive behavior by down-regulating testosterone, which is known to be causally associated with the adoption of calling behavior in Hyla cinerea (3).

In essence, stress is not sexy because high levels of the stress hormone CORT decrease time spent calling and increase the probability of satellite mating behavior. And females don´t like that.

1. Gross, M.R. 1996. Alternative reproductive strategies and tactics: diversity within the sexes. Trends in Ecology and Evolution 11, 92-98.
2. Gerhardt, H.C., Huber, F. 2002. Acoustic Communication in Insects and Anurans. University of Chicago Press, Chicago, Illinois, USA.
3. Burmeister, S.S., Wilczynski, W. 2001. Social context influences androgenic effects on calling in the green treefrog (Hyla cinerea). Hormones and Behavior 40, 550 – 558.

Sarah Crocker

Department of Biology

University of Mississippi

“The Dose Makes the Poison” – Paracelsus

As the average age of the world’s population increases, so does the prevalence of age-related diseases (1). The process of aging, even in healthy individuals, brings with it a multitude of physiological changes throughout the body. Specifically in the brain, the end-result of these physiological changes is a decline in cognitive performance. For many people these changes are too subtle to notice, but for others they can be debilitating. In an attempt to bolster the brain-power of aged individuals, numerous therapeutics have been proposed but few have shown efficacy. One promising target for the treatment of age-related cognitive decline is the endocannabinoid system.

Picture1

A recent publication by a group of researchers from the University of Bonn in Germany suggests that the active compound in cannabis, Δ9-tetrahydrocannabinol (THC), might be beneficial for the aging brain (2). In their study, young and old mice were exposed to a low dose of THC (3mg/kg/day) for 28 days. One week after completing this treatment, the animals’ ability to learn and remember information was tested. Interestingly, month-long exposure to low levels of THC improved the performance of old animals, but impaired the performance of younger animals. Much of the current scientific literature suggests that high doses of THC during adolescence can impair learning and memory, but a select few studies in animals indicate that very low doses may actually improve cognitive function (3). Taken together, these studies hint at a narrow therapeutic window wherein THC may potentially benefit the brain.

Numerous states in the US now allow the medicinal and/or recreational use of cannabis, but its acute and chronic physiological effects remain controversial. As society’s view of cannabis-use evolves, and with the growing concerns posed by an aging population, continued study of THC and its potential benefits on the aging brain warrant further investigation.

The age-old adage posits “everything in moderation,” and in the case of THC’s effects on the brain, this appears to be the case.

1. Trends in aging–United States and worldwide. MMWR Morb Mortal Wkly Rep. 2003;52(6):101-4, 106.

2. Bilkei-gorzo A, Albayram O, Draffehn A, et al. (2017) A chronic low dose of Δ(9)-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nat Med. 23: 782-787.

3. Suliman NA, Taib CNM, Moklas MAM, Basir R. (2017) Delta-9-Tetrahydrocannabinol (∆(9)-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats. Neurotox Res. https://doi.org/10.1007/s12640-017-9806-x 

By Erik Hodges
Biomedical Sciences Department,
University of Mississippi

The Carrot or the Stick? Implications for Neural Mechanisms of Motor Learning

Did you ever learn to play piano? How did your instructor tell you whether your performance was correct or incorrect? Were you chastised for hitting an incorrect note or did you receive a chocolate for every correct note played? The age old idiom ‘By the carrot or by the stick?’ has been contemplated by instructors of all types to motivate their pupils to learn a skill.  Do you dangle a carrot in front of subjects and reward their good behavior or do you threaten them with a “WHACK!” of the punishing stick?

carrot or stick

Researchers have demonstrated that receiving reward or punishment influences different aspects of learning and retention of a motor task (1).  In a recent study, Galea and colleagues used a motor rotation task in which subjects were instructed to hit a target that moved during the task. Subjects in the punishment group lost money (given previously to them) every time they missed the target. Conversely, those in the reward group received money for correct performances. The authors found that those who received punishment learned faster but those who were rewarded retained the motor skill longer.

How does reward or punishment improve motor learning? We know that as a subject gets better at a motor skill, the neuronal circuits in the brain change in the areas associated with motor control (2). This has been evaluated using electroencephalography (EEG) to measure event related potentials (ERPs), which indicate changes in neuronal activity associated with a motor event. (3). Yet how receiving reward and punishment modulates these neuronal changes during motor learning is still unclear.

In the Cognition and Neuromechanics Laboratory (University of Mississippi), we plan to investigate this issue.  Subjects will perform a motor learning task while connected to an EEG system and reward and punishment feedback will be given in the same manner as the study by Galea and colleagues.  Since reward and punishment have shown to produce different effects on motor learning, we expect that they change differently neuronal activity  (i.e. amplitude of ERPs) in areas of the brain related to motor control. The results of this study will helps us better understand how emotion impacts motor learning as well as its neuronal correlates.

1. Galea, J. M., Mallia, E., Rothwell, J., & Diedrichsen, J. (2015). The dissociable effects of punishment and reward on motor learning. Nature neuroscience, 18, 597-602.

2. Dayan, E., & Cohen, L. G. (2011). Neuroplasticity subserving motor skill learning. Neuron, 72, 443–454.

3. MacLean, S. J., Hassall, C. D., Ishigami, Y., Krigolson, O. E., & Eskes, G. A. (2015). Using brain potentials to understand prism adaptation: the error-related negativity and the P300. Frontiers in Human Neuroscience, 9, 335-349.

By Chris Hill
Health and Exercise Science,
University of Mississippi

Making sense of Neuroscience Research

Neuroscience Research, in a broad sense, is a multidisciplinary scientific effort to understand the function of the Nervous System and how it generates behavior. In the last decades, Neuroscience Research has expanded enormously. Multiple methodological approaches have created new specialized fields –from genetic and cellular to behavioral and computational neurosciences. This multilevel approach is exciting! But it also represents a communication challenge, not only for neuroscientists, but also for the general public.

Brain Storm is a platform for researchers (students and senior scientists) to explain their research or comment on the research of others in a way that appeals to both colleagues from different fields and the general public. The philosophy is simple: communicate what you do and learn, and enjoy doing it! Can you make it in 300-400 words? Can you make it interesting and understandable for everyone? Find some tips here

by A.D.

What is Science?

A fire-breathing dragon lives in my garage.’ Suppose (I’m following a group therapy approach by the psychologist Richard Franklin) I seriously make such an assertion to you. Surely you’d want to check it out, see for yourself. There have been innumerable stories of dragons over the centuries, but no real evidence. What an opportunity!

‘Show me,’ you say. I lead you to my garage. You look inside and see a ladder, empty paint ans, an old tricycle – but no dragon.

‘Where’s the dragon?’ you ask.

‘Oh, she’s right here,’ I reply, waving vaguely. ‘I neglected to mention that she’s an invisible dragon.’

You propose spreading flour on the floor of the garage to capture the dragon’s footprints.

‘Good idea,’ I say, ‘but this dragon floats in the air.’

Then you’ll use an infrared sensor to detect the invisible fire.

‘Good idea, but the invisible fire is also heatless.’

You’ll spray-paint the dragon and make her visible.

‘Good idea, except she’s an incorporeal dragon and the paint won’t stick.’

And so on. I counter every physical test you propose with a special explanation of why it won’t work.

Now, what’s the difference between an invisible, incorporeal, floating dragon who spits heatless fire and no dragon at all? If there’s no way to disprove my contention, no conceivable experiment that would count against it, what does it mean to say that my dragon exists? Your inability to invalidate my hypothesis is not at all the same thing as proving it true. Claims that cannot be tested, assertions immune to disproof are veridically worthless, whatever value they may have in inspiring us or in exciting our sense of wonder. What I’m asking you to do comes down to believing, in the absence of evidence, on my say-so.

                                                            “The dragon in my garage”

(The Demon-Haunted world)

By Carl Sagan