NeuroJC

Neuro* Journal Club at the Free University Berlin

Epigenetic control of long term memory specificity in honeybees

ResearchBlogging.org
Recently a study from Ryszard Maleszka’s Lab demonstrates that DNA methylation does play a role in the acquisition of memory and mediates the resistance of this memory to extinction in honeybees (Lockett et al 2010). Now the group of Paul Szyszka in Konstanz provides additional information about the role of DNA methylation in the formation of long term memory.
Using olfactory conditioning of the proboscis extension response (PER), Stephanie Biergans et al. were able to show that DNA methylation mediates the specificity of long term memory, but not short term memory. They trained bees with three odor (conditioned stimulus = CS) – sugar (unconditioned stimulus = US) trials. During this acquisition phase they applied an inhibitor of DNA methylation, Zebularine (blocker of DNA methyltransferase). The bees were tested at different time points afterwards (30 min, 1 day or 3 days) with the trained odor and with an untrained odor. The results show that there is no effect of the inhibitor on the CS memory tests (neither on short term at 30 min nor on long term memory at 1 d or 3 d), traceably the authors conclude that the memory strength is not altered by Zebularin. Nevertheless the data demonstrates that the long term memory is less specific. The specificity was measured as a discrimination index for each bee, calculated as the difference of CS response (1 = PER in test or 0 = no PER) minus the response to an untrained odor (1 = PER in test or 0 = no PER). S. Biergans et al show that these indexes are reduced in Zebularine treated bees compared to bees treated with the vehicle. In other words Zebularine treatment increases the response to the untrained odor; even though this is not exactly what the authors were checking for. In well thought control experiments the people from Konstanz show that the perception of odors in itself is not altered by the drug and importantly that Zebularine does not affect the survival of the bees. Taken these results together the authors suggest that “…different genetic pathways are involved in mediating the strength and discriminatory power of associative odor memories…” (discriminatory power as an elegant synonym for specificity). The question left open (for me) is whether the drug just makes the memory more fuzzy and consequently increases generalization or if there is some other component, for example a non associative component mediated by the US, which is down regulated via DNA methylation during CS-US learning.
Anyway the nice study from Paul Szyszka’s group does not only increase the knowledge about the role of epigenetic mechanism in memory formation, it also highlights the major fact that stimulus specificity is an important issue in investigations concerning the molecular basis of memory formation.

Biergans SD, Jones JC, Treiber N, Galizia CG, & Szyszka P (2012). DNA methylation mediates the discriminatory power of associative long-term memory in honeybees. PloS one, 7 (6) PMID: 22724000

Individual differences in skilled adult readers reveal dissociable patterns of neural activity associated with component processes of reading

ResearchBlogging.orgTo successfully read and understand words one has to master several complex processes. A competent reader not only needs to recognize single letters, he or she must also have knowledge about how these letters are legally combined to larger orthographic units (orthographic processing), how to map these units to sounds (phonological processing) and to associate them with a certain meaning (semantic processing). Previous studies have identified the left ventral temporal region, including ventral extrastriate cortex and the fusiform gyrus to be involved in orthographic processing; left inferior frontal cortex and left temporo-parietal regions to be related to phonological processing and a network consisting of portions of left middle temporal cortex and left inferior frontal cortex as well as the angular gyrus and posterior cingulate cortex to be associated with semantic processing. The aim of the present study was to investigate how these sub-processes are reflected in neural activity depending on individual reading skills. To do so the authors correlated the subjects’ behavioural reading performances assessed by standardized reading measures and their neural activities, which were measured in a series of reading related fMRI-tasks. Besides replicating typical activation patterns associated with the above mentioned sub-processes of reading the present study also found dissociable patterns of brain activity varying in the degree of individual reading skill.


Welcome SE, & Joanisse MF (2012). Individual differences in skilled adult readers reveal dissociable patterns of neural activity associated with component processes of reading. Brain and language, 120 (3), 360-71 PMID: 22281240

Stimulus onset quenches neural variability: a widespread cortical phenomenon

This article focuses on one of the basic properties of the cortical network that is widely considered as noise and mostly averaged out during the experimentation. The neural response is incompletely characterized without focusing on the ongoing activity that apparently gives rise to variable responses to the same stimulus situation. The across-trial membrane potential (Vm) variability and firing rate variability are quantified before and after the onset of the stimulus. Their findings suggest the variability observed is reduced after the stimulus and onset of stimulus improves the stability of the cortical network.

Reference:
Churchland MM, Yu BM, Cunningham JP, Sugrue LP, Cohen MR, Corrado GS, Newsome WT, Clark AM, Hosseini P, Scott BB, Bradley DC, Smith MA, Kohn A, Movshon JA, Armstrong KM, Moore T, Chang SW, Snyder LH, Lisberger SG, Priebe NJ, Finn IM, Ferster D, Ryu SI, Santhanam G, Sahani M, & Shenoy KV (2010). Stimulus onset quenches neural variability: a widespread cortical phenomenon. Nature neuroscience, 13 (3), 369-78 PMID: 20173745

Coffee and Honey bees- Consumption of an acute dose of caffeine reduces acquisition but not memory

ResearchBlogging.org

Not only because I am working with honey bees but because I myself consume an ‘acute’ dose of caffeine every day, I was particularly interested in this new article published in Behavioural brain research this spring having a look on the impact caffeine consumption has on learning and memory in Honey bees. The experiments follow a nice line of arguments answering upcoming questions right away with the next experiment and leave you at the end with almost no questions.

So far studies supporting the influence of caffeine on learning and memory are inconsistent: some show memory improvement after caffeine consumption whereas others report that caffeine ingestion has little or no effect on learning and memory in invertebrates. In particular in Honey bees caffeine had no effect on acquisition, but increased long term memory retention in an appetitive visual learning task whereas in experiments using Drosophila caffeine decreased acquisition. The authors argue that the differences may be a result of the different treatment: Flies consumed the caffeine while in bees the caffeine was delivered through the cuticle or via injection. Also in Drosophila an aversive stimulus was used during conditioning, whereas the bees were conditioned using an appetitive reward. Consequentially the authors investigate the effects of caffeine ingestion in Honey bees on acquisition and memory recall using olfactory appetitive learning.
In their first set of experiments they test whether ingesting caffeine during conditioning influences the rate of acquisition and memory recall and demonstrate that caffeine reduces the level of response to the conditioned odor. However a memory recall 24 hours later revealed that “the reduction in response observed during acquisition was not due to a failure of the bees to acquire the odor-reward association, as the majority of bees in each treatment responded to the odor as if it predicted reward.” Raising the question, if the reduction in the expression of the conditioned response during acquisition may be due to the bitter taste of caffeine? The authors rule out this possibility by feeding caffeine prior to conditioning with the same experimental outcome as before. Bringing the authors to the next question: Is the reduction in response levels during acquisition due to caffeine reducing motivation? Consumption of caffeine could possibly reduce the motivation for consumption of the sugar-reward either by producing malaise or by making the bees feel satiated. To examine this possibility, in a following experiment bees were given a dose of sucrose containing different caffeine concentrations but no differences in the amount of subsequent taken sucrose solution were observed.
In the last experiment the effect of caffeine on recall fed after acquisition is examined showing that caffeine does not influence post-acquisition consolidation processes. In summary the data suggest an effect of caffeine on acquisition without an effect on the one day later recall.
As an explanation for their results the authors suggest an increased calcium level as previous studies showed that injection of caffeine into the hemolymph increases calcium levels in the honey bee brain. They argue that ’in Drosophila, inhibition of protein kinase C (PKC) activity was shown to reduce the expression of the learned behavior (a reduction in courting of a mated female by a male fly) during the acquisition phase’. Similar to the present experiments the males with reduced PKC activity performed the same as control flies during memory tests indicating that they had learned. The authors suggest a following experiment to provide insight into the role of calcium signaling in the effects of caffeine on learning by mimicking the consequences of caffeine ingestion by increasing calcium levels during acquisition.

Finally after reading this article I am no more concerned about the coffee I was drinking during the preparation of my talk. I may not remember everything in 5 minutes but tomorrow I will be as good as any non coffee drinking talk-giver. That holds true obviously at least for bees!

Mustard JA, Dews L, Brugato A, Dey K, & Wright GA (2012). Consumption of an acute dose of caffeine reduces acquisition but not memory in the honey bee. Behavioural brain research, 232 (1), 217-224 PMID: 22521838

OctßR1 and OctßR2 act antagonistically on starvation induced locomotor speed and synaptic growth in Drosophila larvae

The authors’ previous paper Koon et al. (2011) presented in JC in March last year, demonstrated structural changes in octopaminergic synaptic terminals in response to starvation. These changes induce an increase in locomotion. Underlying the structural change is the activation of a positive-feedback mechanism, in which octopamine release, presumably by type II octopaminergic synaptic boutons, activates octopamine autoreceptors Octß2R. In turn, Octß2R turns on a cAMP- and CREB-dependent signaling cascade at octopaminergic neurons, which induces synaptic expansion.

In their new paper (May 2012), they report the presence of an alternative octopamine autoreceptor Octß1R. That receptor has opposed functions on synaptic growth. Mutations in octß1r result in the overgrowth of both glutamatergic and octopaminergic neuromuscular junctions (NMJs). Octß1R is suggested to function in a cell-autonomous manner at presynaptic motorneurons (like Octß2R) and likely inhibits cAMP production through inhibitory Go (unlike Octß2R). Octß1R is required for acute changes in synaptic structure in response to octopamine and for starvation-induced increase in locomotor speed (like Octß2R). Any paracrine stimulation of type I boutons’ growth as it was found for the Octß2R is not mentioned for Octß1R.

This paper shows a antagonistic action of one neurotransmitter on synaptic growth depending on the receptor it is binding to.

Koon, A., & Budnik, V. (2012). Inhibitory Control of Synaptic and Behavioral Plasticity by Octopaminergic Signaling Journal of Neuroscience, 32 (18), 6312-6322 DOI: 10.1523/JNEUROSCI.6517-11.2012
ResearchBlogging.org

NPY and olfactory response in Axolotls salamander.

I read this quite old paper, because of a blog post (on reasearch blogging), made me think that this paper showed that the response of olfactory receptor neurons were changing with starvation state of the animal. This is not the case and indeed the blog was not arguing directly that, I misinterpreted the post…

Mousley et al. looked at NPY (one neuropeptide involved in feeding behavior) in their favorite salamender Ambystoma mexicanum. They use an antibody against porcine NPY to localize the neuropeptide in the salamender CNS, use RACE to determine the actual NPY sequence of the axolotls, and use in vivo EOG and in vitro patch clamp on olfactory epithelium neurons (in slides) to asseess the effect of NPY application on the response of olfactory receptor neurons (apparently).

They could find a greater inward current and EOG signal in response to a specific odor, after adding NPY in hungry animals (or slices from hungry animals) but smaller effects (or none) in fed animals. They conclude that starvation may change the expression of NPY receptors (or other part of the NPY pathway) in the olfactory epithelium.

This sounds interesting, and the whole is difficult to critisize, also because difficult to understand/follow: for instance, the anatomy (fig1 and 2) cannot be understood by non-specialists. In general, the logic of certain experiments are difficult to grasp (Fig. 7 for instance)

In addition:

1. they say there is no NPY labelling in the olfactory epithelium.

2. there is no difference in activity between fed and non-fed.

3. the NPY effect goes down after 10 min of application and washing is not making it disappear.

the question : is the NPY effect an artefact? is not taken discussed, although the results are kind of ambiguous.

Mousley, A. (2006). Terminal Nerve-Derived Neuropeptide Y Modulates Physiological Responses in the Olfactory Epithelium of Hungry Axolotls (Ambystoma mexicanum) Journal of Neuroscience, 26 (29), 7707-7717 DOI: 10.1523/JNEUROSCI.1977-06.2006

No need for cognitive maps in insects?

ResearchBlogging.orgIn many animals the ability to navigate over long distances is an important prerequisite for foraging, including ants and bees. The use of path integration(PI) is widely accepted, however the questions of to what extent the path integration can help navigation and if a higher form of inner global representation called “cognitive map” is really existing are still under debate. This paper presents an artificial memory system which is based on path integration and various landmark guidance mechanisms,and used some real animal experimental data into their artificial memory system, in order to show that the “cognitive map” is not necessary, cause the PI and landmark in their artificial memory system can guide the entire work of navigation in ants and bees.


Cruse, H., & Wehner, R. (2011). No Need for a Cognitive Map: Decentralized Memory for Insect Navigation PLoS Computational Biology, 7 (3) DOI: 10.1371/journal.pcbi.1002009

Dopaminergic Modulation of Sucrose Acceptance Behavior in Drosophila

Prof. Jochen Pflüger will present the following paper on Monday (17/04):

ResearchBlogging.org
Marella, S., Mann, K., & Scott, K. (2012). Dopaminergic Modulation of Sucrose Acceptance Behavior in Drosophila Neuron, 73 (5), 941-950 DOI: 10.1016/j.neuron.2011.12.032

The generation of a memory trace?

ResearchBlogging.org

Have you seen the movie Inception? If not you should. It is all about a group of people high jacking the dreams of company bosses to steal useful information from their memory to sell them to their rivals. Anyway the Holy Grail of these “being in other peoples head and manipulating things” – trips is not the stealing but rather the INCEPTION of a new memory.

Now a study from the Mark Mayford lab (Garner et al 2012) has shown a way to generate a synthetic memory in rodents by a smart combination of genetic tricks and behavioral assay. They used double transgenic mice in which they can switch on and off the activity dependent expression (regulated by a c-fos promoter) of an hM3Dq-receptor. Activating this receptor by the injection of its agonist (CNO) induced neural activity.

They took these mice, switched on the activity regulated expression of the receptor and put them into a novel context (ctxA). Consequently they assume that the receptor will be expressed in those neurons activated throughout ctxA exploration. On the consecutive day, when the receptor expression is switched off, they fear conditioned the animals in a second context (ctxB) under the influence of the receptor agonist CNO. By injecting CNO the authors claim that they fire the neurons active in the pre exposure of ctxA while fear conditioning ctxB. In the following retrieval test the mere ctxB exposure could not elicit fear response (freezing). Nevertheless when animals were treated with CNO and tested in ctxB, freezing was on the level of the control animals. Since no fear response was observed in ctxA irrespectively of CNO injection the authors postulate that a “…hybrid representation incorporating both CNO-induced artificial stimulation and natural sensory cues…” was learned. Additional control experiments showed that the effect on the memory formation is specific for the pre exposed context. Further the authors demonstrated that if CNO was not injected during training but during retrieval memory retention for ctxB is reduced suggesting CNO is inducing a competing signal.

In sum Garner et al produced a synthetic memory trace by adding specific neural activity to the neural activity caused by sensory input in the presence of reinforcement. Despite the promising title: “Generation of a Synthetic Memory Trace” it seems to be a long way to a complete INCEPTION of a memory trace. Anyway the work might be an important step towards understanding of the role of internal generated neural activity during the formation of a memory produced by external stimuli.

Garner AR, Rowland DC, Hwang SY, Baumgaertel K, Roth BL, Kentros C, & Mayford M (2012). Generation of a synthetic memory trace. Science (New York, N.Y.), 335 (6075), 1513-6 PMID: 22442487

Functional neurogenesis induced by operant but not by classical conditioning

ResearchBlogging.orgSome studies on olfactory conditioning in rodents have shown that long term memory of the conditioned odor depends on neurogenesis, while other studies did not detect such a dependence on neurogenesis. In their paper entitled „Involvement of Newborn Neurons in Olfactory Associative Learning? The Operant or Non-operant Component of the Task Makes All the Difference“, Mandairon et al. make the interesting discovery that neurogenesis in the olfactory bulb is dependent on the procedure by which experimental animal learn to distinguish two odors, providing a potential explanation for the discrepancy between the previous studies. The authors set up an operant conditioning paradigm where the animals could explore two differently scented boxes, only one of which contained a sucrose reward. In the non-operant or classical experiment, the animals were trained with only one box and one odor that alternatingly either contained odor A and no sucrose or odor B and sucrose. While the operant animals received sucrose throughout the 5 days of training, the classical animals were presented with a choice of two boxes each with one of the two odors on the final day. The choices of both animal groups were then tallied and compared. Each of these two groups had a matched ‘pseudo-conditioned’ group in which there was a random association between odor and sucrose, such that no odor was predictive of the sucrose.

The authors then sacrificed the animals after the final experimental day and used BrdU staining to screen for newborn neurons in the olfactory bulb. The functionality of these neurons was tested by detecting the immediate-early gene Zif. The authors found a higher density of BrdU-stained neurons in the olfactory bulb of operantly trained neurons compared with their pseudo-conditioned control group, while there was no such difference between the two classical groups. However, presumably because the trial duration was set to be higher in the classical conditioning paradigm, both classical groups had a higher density of BrdU-stained neurons than their respective operant groups. The percentage of active newborn neurons was also larger in the operant vs. its control group, while no such difference was found in the classical groups. This difference in functional neurogenesis was not due to generally higher activation in the experimental vs. the pseudoconditioned groups, as overall activation was similar across all groups.
Finally, the authors found higher brain activation levels in the orbital cortex for the operant group and in the infralimbic cortex for the classical group, further supporting the different behavioral requirements in the two conditioning procedures.

These results not only could potentially help explain the varying results when the necessity for neurogenesis is tested in olfactory conditioning experiments, but could also pave the way for studies into why operant learning is always more effective than classical conditioning (learning-by-doing, generation effect), despite the fact that both groups are learning he same thing.


Mandairon, N., Sultan, S., Nouvian, M., Sacquet, J., & Didier, A. (2011). Involvement of Newborn Neurons in Olfactory Associative Learning? The Operant or Non-operant Component of the Task Makes All the Difference Journal of Neuroscience, 31 (35), 12455-12460 DOI: 10.1523/JNEUROSCI.2919-11.2011