The malleable brain: plasticity of neural circuits and behavior: A review from students to students

One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation (LTP) and long-term depression (LTD) respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by LTP and LTD, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity.Fil: Schaefer, Natascha. University of Wuerzburg; AlemaniaFil: Rotermund, Carola. University of Tuebingen; AlemaniaFil: Blumrich, Eva Maria. Universitat Bremen; AlemaniaFil: Lourenco, Mychael V.. Universidade Federal do Rio de Janeiro; BrasilFil: Joshi, Pooja. Robert Debre Hospital; FranciaFil: Hegemann, Regina U.. University of Otago; Nueva ZelandaFil: Jamwal, Sumit. ISF College of Pharmacy; IndiaFil: Ali, Nilufar. Augusta University; Estados UnidosFil: García Romero, Ezra Michelet. Universidad Veracruzana; MéxicoFil: Sharma, Sorabh. Birla Institute of Technology and Science; IndiaFil: Ghosh, Shampa. Indian Council of Medical Research; IndiaFil: Sinha, Jitendra K.. Indian Council of Medical Research; IndiaFil: Loke, Hannah. Hudson Institute of Medical Research; AustraliaFil: Jain, Vishal. Defence Institute of Physiology and Allied Sciences; IndiaFil: Lepeta, Katarzyna. Polish Academy of Sciences; ArgentinaFil: Salamian, Ahmad. Polish Academy of Sciences; ArgentinaFil: Sharma, Mahima. Polish Academy of Sciences; ArgentinaFil: Golpich, Mojtaba. University Kebangsaan Malaysia Medical Centre; MalasiaFil: Nawrotek, Katarzyna. University Of Lodz; ArgentinaFil: Paid, Ramesh K.. Indian Institute of Chemical Biology; IndiaFil: Shahidzadeh, Sheila M.. Syracuse University; Estados UnidosFil: Piermartiri, Tetsade. Universidade Federal de Santa Catarina; BrasilFil: Amini, Elham. University Kebangsaan Malaysia Medical Centre; MalasiaFil: Pastor, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Wilson, Yvette. University of Melbourne; AustraliaFil: Adeniyi, Philip A.. Afe Babalola University; NigeriaFil: Datusalia, Ashok K.. National Brain Research Centre; IndiaFil: Vafadari, Benham. Polish Academy of Sciences; ArgentinaFil: Saini, Vedangana. University of Nebraska; Estados UnidosFil: Suárez Pozos, Edna. Instituto Politécnico Nacional; MéxicoFil: Kushwah, Neetu. Defence Institute of Physiology and Allied Sciences; IndiaFil: Fontanet, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Turner, Anthony J.. University of Leeds; Reino Unid

The Effects of Neurocognitive Aging on Sentence Processing

Across the lifespan, successful language comprehension is crucial for continued participation in everyday life. The success of language comprehension relies on the intact functioning of both language-specific processes as well as domain-general cognitive processes that support language comprehension in general. This two-sided nature of successful language comprehension may contribute to the two diverging observations in healthy aging: the preservation and the decline of language comprehension on both the cognitive and the neural level. To date, our understanding of these two competing facets is incomplete and unclear. While greater language experience comes with increasing age, most domain-general cognitive functions, like verbal working memory, decline in healthy aging. The here presented thesis shows that when the electrophysiological network relevant for verbal working memory is already compromised at rest, language comprehension declines in older adults. Moreover, it could be shown that, as verbal working memory capacity declines with age, resources may be- come insufficient to successfully encode language-specific information into memory, yielding language comprehension difficulties in old age. Age differences in the electrophysiological dynamics underlying sentence encoding indicate that the encoding of detailed information may increasingly be inhibited throughout the lifespan, possibly to avoid overloading the verbal working memory. However, limitations in verbal working memory could be attenuated by the use of language-specific constraints. That is, semantic and syntactic constraints can be used to establish relations between words which reduces the memory load from individual word information to information about word group. Here, it was found that older adults do not benefit from the use of syntactic constraints as much as younger adults while the benefit of using semantic constraints was comparable across age. Overall, the here presented thesis suggests that previous findings on language comprehension in healthy aging are not contradictory but rather converge on a simultaneous combination of selective preservation and decline of various language-specific processes, burdened by domain-general neurocognitive aging

Memory Performance in Children with Temporal Lobe Epilepsy: Neocortical vs. Dual Pathologies

This study investigated memory in children with temporal lobe epilepsy and the ability to discern hippocampal dysfunction with conventional memory tests that are typically used to detect more global memory impairment. All data was obtained retrospectively from the epilepsy surgery program at a local children’s hospital. The research population consisted of 54 children with intractable epilepsy of temporal onset, balanced across pathology types (with and without hippocampal disease) and other demographics. Each was given a clinical battery prior to surgical intervention, which included the WRAML/WRAML2 Verbal Learning subtest from which the dependent variables for this study were extracted. The research hypothesis had predicted that memory retention between verbal learning and recall would be worse for participants with pathology that included hippocampal sclerosis than for those with non-hippocampal temporal lobe pathology. A two-way mixed-design ANOVA was used to test the hypothesis, which allowed incorporation of variables of interest related to memory factors, pathology type, and hemispheric laterality, as well as their various interactions. There was a significant main effect for change in the number of words retained from the final learning trial to the delayed recall. Although the interaction between memory retention and pathology type was not statistically significant, the average of the memory scores as it related to pathology by side did show significance. Thus, results did not support the hypothetical relationship between retention and hippocampal function. However, additional exploratory analyses revealed that the final learning trial by itself was associated with hippocampal pathology, which applied only to those participants with left-hemisphere lesions. Logistic regression with the final learning trial correctly classified 74 percent of participants into the appropriate pathology category, with 81 percent sensitivity to hippocampal dysfunction. Mean participant memory scores were nearly one standard deviation below the normative mean for both delayed recall and total learning scaled scores, regardless of pathology type or lesion hemisphericity. Thus, while the conventionally used indices of the WRAML Verbal Learning test are useful for determining overall memory status, they are not specific to pathological substrate. The within-subject main effect showed an expected loss of information across the time of the delay, but overall the recall score showed no association with hippocampal functioning. This study revealed the possibility of measuring hippocampal function at statistically significant group levels using learning scores from a widely used measure of verbal memory, even in participants with intact contralateral mesial temporal structures. It also indicated that hippocampal structures do not play a role during recall measures given after a standard time delay. Data further demonstrated a role of the hippocampus for encoding and transferring information beyond short term/working memory into long term. During the learning process, the hippocampus appears to work in concert with short-term memory systems, but does not take over the encoding process until enough repetitions have occurred to saturate the working memory buffer. This research represents a small, yet important step forward in our understanding of the hippocampus, with potentially important implications for the future study of memory constructs and mensuration

Neurofly 2008 abstracts : the 12th European Drosophila neurobiology conference 6-10 September 2008 Wuerzburg, Germany

This volume consists of a collection of conference abstracts

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40

Language learning in aphasia: A narrative review and critical analysis of the literature with implications for language therapy

People with aphasia (PWA) present with language deficits including word retrieval difficulties after brain damage. Language learning is an essential life-long human capacity that may support treatment-induced lan-guage recovery after brain insult. This prospect has motivated a growing interest in the study of language learning in PWA during the last few decades. Here, we critically review the current literature on language learning ability in aphasia. The existing studies in this area indicate that (i) language learning can remain functional in some PWA, (ii) inter-individual variability in learning performance is large in PWA, (iii) language processing, short-term memory and lesion site are associated with learning ability, (iv) preliminary evidence suggests a relationship between learning ability and treatment outcomes in this population. Based on the reviewed evidence, we propose a potential account for the interplay between language and memory/learning systems to explain spared/impaired language learning and its relationship to language therapy in PWA. Finally, we indicate potential avenues for future research that may promote more cross-talk between cognitive neuro-science and aphasia rehabilitation

Brain Rhythms and Working Memory in Healthy Ageing

Working memory (WM), the ability to maintain and manipulate information to guide immediate cognitive processing, is vulnerable to age-related decline. Compared with younger adults, older adults demonstrate smaller WM capacities, a decrease in the ability to manipulate items held in WM, and a greater susceptibility to interference from distracting information. However, the neural underpinnings of WM decline in normal ageing are unclear. One technique that can be used to investigate the neurophysiological processes underlying cognition is electroencephalography (EEG), which non-invasively records activity from the awake human brain. The research described in this thesis uses EEG to investigate the neurophysiology of WM in healthy younger and older adults, with a particular focus on neural oscillatory activity in the alpha frequency range (8-12 Hz). As such, Chapter 1 consists of a review of the literature relevant to use of EEG to investigate the neurophysiology of WM performance in younger and older adults. WM performance deficits in older adults are particularly salient under increasing WM loads. Alpha oscillations have been shown to support verbal WM performance under high loads in younger adults, so the aim of Chapter 2 was to investigate the load-dependent modulation of alpha oscillatory power and frequency in younger and older adults during verbal WM. No age differences in verbal WM performance were found, and alpha power and alpha peak frequency were modulated in a similar task- and load-dependent manner in both younger and older adults. Another factor influencing WM performance in older adults is a decline in selective attention. Older adults perform worse on and are less able to modulate alpha power than younger adults in tasks involving cues about ‘where’ or ‘when’ a memory set will appear. The study described in Chapter 3 investigated whether providing cues towards memory set presentation time led to enhanced selective attention before the onset of the memory set, as indexed by alpha oscillatory activity. Predictive cues led to improved WM performance in both age groups, but alpha power in preparation of the memory set did not influence task performance. In Chapter 3, there were no age differences in WM performance when manipulating memory set presentation time. However, processing speed may not only limit the speed at which items are encoded into WM, but also the speed at which stimuli are transformed into a stable memory representation (i.e., WM consolidation). Therefore, the study contained in Chapter 4 investigated age differences in the ability to consolidate items into visual WM. In this study, older adults demonstrated poorer WM performance and slower consolidation at low WM loads, providing evidence for altered visual WM consolidation with age. Finally, visual WM is severely limited in capacity, highlighting the importance of encoding task-relevant information while ignoring distractors. The modulation of alpha oscillatory power has been implicated in the inhibition of distractors during WM in younger adults, but it is unclear if alpha power modulation also supports distractor inhibition in older adults. The study described in Chapter 5 investigated age differences in alpha oscillatory power before the onset of distractors during the visual WM retention period. Although there were no age differences in WM performance, younger adults demonstrated functionally relevant increases in alpha power before distractors, while older adults showed decreases in alpha power. Therefore, younger and older adults likely use different neural strategies to inhibit distractors during WM performance. Taken together, the results of the studies contained in this thesis provide further evidence for age-related changes to neural oscillatory activity, particularly in the alpha frequency band, even when age differences in WM performance are not present. These findings may have important implications for providing novel targets for detecting or preventing age-related cognitive decline.Thesis (Ph.D.) -- University of Adelaide, School of Biomedicine, 202