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

Financial distress prediction using the hybrid associative memory with translation

This paper presents an alternative technique for financial distress prediction systems. The method is based on a type of neural network, which is called hybrid associative memory with translation. While many different neural network architectures have successfully been used to predict credit risk and corporate failure, the power of associative memories for financial decision-making has not been explored in any depth as yet. The performance of the hybrid associative memory with translation is compared to four traditional neural networks, a support vector machine and a logistic regression model in terms of their prediction capabilities. The experimental results over nine real-life data sets show that the associative memory here proposed constitutes an appropriate solution for bankruptcy and credit risk prediction, performing significantly better than the rest of models under class imbalance and data overlapping conditions in terms of the true positive rate and the geometric mean of true positive and true negative rates.This work has partially been supported by the Mexican CONACYT through the Postdoctoral Fellowship Program [232167], the Spanish Ministry of Economy [TIN2013-46522-P], the Generalitat Valenciana [PROMETEOII/2014/062] and the Mexican PRODEP [DSA/103.5/15/7004]. We would like to thank the Reviewers for their valuable comments and suggestions, which have helped to improve the quality of this paper substantially

Gene selection and disease prediction from gene expression data using a two-stage hetero-associative memory

In general, gene expression microarrays consist of a vast number of genes and very few samples, which represents a critical challenge for disease prediction and diagnosis. This paper develops a two-stage algorithm that integrates feature selection and prediction by extending a type of hetero-associative neural networks. In the first level, the algorithm generates the associative memory, whereas the second level picks the most relevant genes.With the purpose of illustrating the applicability and efficiency of the method proposed here, we use four different gene expression microarray databases and compare their classification performance against that of other renowned classifiers built on the whole (original) feature (gene) space. The experimental results show that the two-stage hetero-associative memory is quite competitive with standard classification models regarding the overall accuracy, sensitivity and specificity. In addition, it also produces a significant decrease in computational efforts and an increase in the biological interpretability of microarrays because worthless (irrelevant and/or redundant) genes are discarded

The functional role of dreaming in emotional processes

Dream experience (DE) represents a fascinating condition linked to emotional processes and the human inner world. Although the overlap between REM sleep and dreaming has been overcome, several studies point out that emotional and perceptually vivid contents are more frequent when reported upon awakenings from this sleep stage. Actually, it is well-known that REM sleep plays a pivotal role in the processing of salient and emotional waking-life experiences, strongly contributing to the emotional memory consolidation. In this vein, we highlighted that, to some extent, neuroimaging studies showed that the processes that regulate dreaming and emotional salience in sleep mentation share similar neural substrates of those controlling emotions during wakefulness. Furthermore, the research on EEG correlates of the presence/absence of DE and the results on EEG pattern related to the incorporated memories converged to assign a crucial role of REM theta oscillations in emotional re-processing. In particular, the theta activity is involved in memory processes during REM sleep as well as during the waking state, in line with the continuity hypothesis. Also, the gamma activity seems to be related to emotional processes and dream recall as well as to lucid dreams. Interestingly, similar EEG correlates of DE have been found in clinical samples when nightmares or dreams occur. Research on clinical samples revealed that promoting the rehearsal of frightening contents aimed to change them is a promising method to treat nightmares, and that lucid dreams are associated with an attenuation of nightmares. In this view, DE can defuse emotional traumatic memories when the emotional regulation and the fear extinction mechanisms are compromised by traumatic and frightening events. Finally, dreams could represent a sort of simulation of reality, providing the possibility to create a new scenario with emotional mastery elements to cope with dysphoric items included in nightmares. In addition, it could be hypothesized that the insertion of bizarre items besides traumatic memories might be functional to “impoverish” the negative charge of the experiences

A computational account of threat-related attentional bias

Visual selective attention acts as a filter on perceptual information, facilitating learning and inference about important events in an agent’s environment. A role for visual attention in reward-based decisions has previously been demonstrated, but it remains unclear how visual attention is recruited during aversive learning, particularly when learning about multiple stimuli concurrently. This question is of particular importance in psychopathology, where enhanced attention to threat is a putative feature of pathological anxiety. Using an aversive reversal learning task that required subjects to learn, and exploit, predictions about multiple stimuli, we show that the allocation of visual attention is influenced significantly by aversive value but not by uncertainty. Moreover, this relationship is bidirectional in that attention biases value updates for attended stimuli, resulting in heightened value estimates. Our findings have implications for understanding biased attention in psychopathology and support a role for learning in the expression of threat-related attentional biases in anxiety

Mammalian Brain As a Network of Networks

Acknowledgements AZ, SG and AL acknowledge support from the Russian Science Foundation (16-12-00077). Authors thank T. Kuznetsova for Fig. 6.Peer reviewedPublisher PD

Dopamine Modulation of Emotional Learning in the Medial Prefrontal Cortex

Dopamine (DA) transmission plays a critical role in the processing of emotionally salient information and in associative learning and memory processes. Within the mammalian brain, neurons within the medial prefrontal cortex (mPFC) are involved critically in the encoding, expression, and extinction of emotionally salient learned information. Within the mPFC, DAergic transmission is involved importantly in controlling attention related and motivational processes, particularly within the context of emotionally salient sensory information. Considerable evidence suggests differential roles for DA D1-like versus D2-like receptors, including the D4-receptor subtype, in the regulation of neuronal activity and emotional processing within the mPFC. Using behavioural models of emotional learning and memory in rats, including olfactory fear-conditioning and conditioned place preference assays, we compared the roles of DA D1-receptor versus D4-receptor activation during the encoding and recall phases of emotional learning and memory. We report that specific activation of DA D4-receptors within the mPFC strongly potentiates the salience of normally nonsalient emotional associative fear memories and blocks the encoding of suprathreshold conditioned fear associations and has no effect on memory recall. In addition, the bidirectional effect demonstrated by D4-receptor activation in the mPFC depends upon downstream signaling via CaMKII, cyclic-AMP/PKA, and PP1 substrates In contrast, intra-mPFC D1-receptor activation failed to increase the emotional salience of subthreshold fear stimuli but completely blocked the expression of previously learned aversive and rewarding memories. Interestingly, both intra-PLC D1-receptor mediated block of either fear-related or reward-related associative memories were dependent upon downstream cAMP signaling as both effects were rescued by co-administration of a cAMP inhibitor. Taken together these results demonstrate that DA D4 versus D1 subtype receptor transmission within the mPFC plays distinct functional roles in the processing of emotionally salient versus nonsalient associative information and differentially modulates the encoding versus recall phases of emotional memory within the mPFC through distinct molecular signaling pathways. A clearer understanding of the specific roles of DA D1 and D4 receptor transmission during emotional learning and memory may help elucidate how abnormalities in the mPFC neural circuitry may lead to aberrant associative learning and memory processes in disorders such as schizophrenia, drug addiction, PTSD and ADHD

The gut-brain axis, BDNF, NMDA and CNS disorders

Gastro-intestinal (GI) microbiota and the ‘gut-brain axis’ are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-d-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders

Memory formation shaped by astroglia

Astrocytes, the most heterogeneous glial cells in the central nervous system (CNS), execute a multitude of homeostatic functions and contribute to memory formation. Consolidation of synaptic and systemic memory is a prolonged process and hours are required to form long-term memory. In the past, neurons or their parts have been considered to be the exclusive cellular sites of these processes, however, it has now become evident that astrocytes provide an important and essential contribution to memory formation. Astrocytes participate in the morphological remodeling associated with synaptic plasticity, an energy-demanding process that requires mobilization of glycogen, which, in the CNS, is almost exclusively stored in astrocytes. Synaptic remodeling also involves bidirectional astroglial-neuronal communication supported by astroglial receptors and release of gliosignaling molecules. Astroglia exhibit cytoplasmic excitability that engages second messengers, such as Ca(2+), for phasic, and cyclic adenosine monophosphate (cAMP), for tonic signal coordination with neuronal processes. The detection of signals by astrocytes and the release of gliosignaling molecules, in particular by vesicle-based mechanisms, occurs with a significant delay after stimulation, orders of magnitude longer than that present in stimulus–secretion coupling in neurons. These particular arrangements position astrocytes as integrators ideally tuned to support time-dependent memory formation