The effects of dynamical synapses on firing rate activity: a spiking neural network model.

Accumulating evidence relates the fine-tuning of synaptic maturation and regulation of neural network activity to several key factors, including GABAA signaling and a lateral spread length between neighboring neurons (i.e., local connectivity). Furthermore, a number of studies consider short-term synaptic plasticity (STP) as an essential element in the instant modification of synaptic efficacy in the neuronal network and in modulating responses to sustained ranges of external Poisson input frequency (IF). Nevertheless, evaluating the firing activity in response to the dynamical interaction between STP (triggered by ranges of IF) and these key parameters in vitro remains elusive. Therefore, we designed a spiking neural network (SNN) model in which we incorporated the following parameters: local density of arbor essences and a lateral spread length between neighboring neurons. We also created several network scenarios based on these key parameters. Then, we implemented two classes of STP: (1) short-term synaptic depression (STD) and (2) short-term synaptic facilitation (STF). Each class has two differential forms based on the parametric value of its synaptic time constant (either for depressing or facilitating synapses). Lastly, we compared the neural firing responses before and after the treatment with STP. We found that dynamical synapses (STP) have a critical differential role on evaluating and modulating the firing rate activity in each network scenario. Moreover, we investigated the impact of changing the balance between excitation (E) and inhibition (I) on stabilizing this firing activity.

Role of Anterior Cingulate Cortex in Instrumental Learning: Blockade of Dopamine D1 Receptors Suppresses Overt but Not Covert Learning.

HIGHLIGHTS Blockade of dopamine D1 receptors in ACC suppressed instrumental learning when overt responding was required.Covert learning through observation was not impaired.After treatment with a dopamine antagonist, instrumental learning recovered but not the rat's pretreatment level of effort tolerance.ACC dopamine is not necessary for acquisition of task-relevant cues during learning, but regulates energy expenditure and effort based decision. Dopamine activity in anterior cingulate cortex (ACC) is essential for various aspects of instrumental behavior, including learning and effort based decision making. To dissociate learning from physical effort, we studied both observational (covert) learning, and trial-and-error (overt) learning. If ACC dopamine activity is required for task acquisition, its blockade should impair both overt and covert learning. If dopamine is not required for task acquisition, but solely for regulating the willingness to expend effort for reward, i.e., effort tolerance, blockade should impair overt learning but spare covert learning. Rats learned to push a lever for food rewards either with or without prior observation of an expert conspecific performing the same task. Before daily testing sessions, the rats received bilateral ACC microinfusions of SCH23390, a dopamine D1 receptor antagonist, or saline-control infusions. We found that dopamine blockade suppressed overt responding selectively, leaving covert task acquisition through observational learning intact. In subsequent testing sessions without dopamine blockade, rats recovered their overt-learning capacity but not their pre-treatment level of effort tolerance. These results suggest that ACC dopamine is not required for the acquisition of conditioned behaviors and that apparent learning impairments could instead reflect a reduced level of willingness to expend effort due to cortical dopamine blockade.

How Knowledge of Ancient Egyptian Women Can Influence Today's Gender Role: Does History Matter in Gender Psychology?

A gender role is a set of societal norms dictating what types of behaviors are considered desirable or appropriate for a person based on their sex. However, socially constructed gender roles can lead to equal rights between genders but also to severe disadvantages and discrimination with a remarkable variety between different countries. Based on social indicators and gender statistics, "women in the Arab region are on average more disadvantaged economically, politically, and socially than women in other regions." According to Banduras' social learning theory, we argue that profound knowledge of the historical contributions of Ancient Egyptian female pioneers in science, arts, and even in ruling Egypt as Pharaohs can improve today's gender role in Egypt and Middle Eastern countries. Therefore, this article provides an elaborate review of the gender role of women in Ancient Egypt, outlining their prominence, influence, and admiration in ancient societies, and discusses the possible psychological impact of this knowledge on today's gender role. We suggest that future empirical research should investigate how enhancing the knowledge of women from Ancient Egypt can improve today's gender role in Egypt and the Middle East. Bandura's social learning theory is outlined as a possible framework for future research.

Acquired equivalence associative learning in GTC epileptic patients: experimental and computational study.

Previous cognitive behavioral studies based on Acquired Equivalence Associative learning Task (AEALT) showed a strong relation between hippocampus and basal ganglia in associative learning. However, experimental behavioral studies of patients with Generalized Tonic Clonic (GTC) epilepsy remained sparse. The aim of the present study is to integrate a classical behavioral cognitive analysis with a computational model approach to investigate cognitive associative learning impairments in patients with GTC epilepsy. We measured the accuracy of associative learning response performance in five GTC epileptic patients and five control subjects by using AEALT, all subjects were matched in age and gender. We ran the task using E-Prime, a neuropsychological software program, and SPSS for data statistical analysis. We tested whether GTC epileptic patients would have different learning performance than normal subjects, based on the degree and the location of impairment either in basal ganglia and/or hippocampus. With the number of patients that was available, our behavioral analysis showed no remarkable differences in learning performance of GTC patients as compared to their control subjects, both in the transfer and acquisition phases. In parallel, our simulation results confirmed strong connection and interaction between hippocampus and basal ganglia in our GTC and their control subjects. Nevertheless, the differences in neural firing rate of the connectionist model and weight update of basal ganglia were not significantly different between GTC and control subjects. Therefore, the behavioral analysis and the simulation data provided the same result, thus indicating that the computational model is likely to predict cognitive outcomes.

Distribution of nitric oxide-producing cells along spinal cord in urodeles.

Nitric oxide is a unique neurotransmitter, which participates in many physiological and pathological processes in the organism. There are little data about the neuronal nitric oxide synthase immunoreactivity in the spinal cord of amphibians. In this respect, the present study aims to investigate the distribution of nitric oxide producing cells in the spinal cord of urodele and to find out the possibility of a functional locomotory role to this neurotransmitter. The results of the present study demonstrate a specific pattern of NADPH-d labeling in the selected amphibian model throughout the spinal cord length as NADPH-d-producing cells and fibers were present in almost all segments of the spinal cord of the salamander investigated. However, their number, cytological characteristics and labeling intensity varied significantly. It was noticed that the NO-producing cells (NO-PC) were accumulated in the ventral side of certain segments in the spinal cord corresponding to the brachial and sacral plexuses. In addition, the number of NO-PC was found to be increased also at the beginning of the tail and this could be due to the fact that salamanders are tetrapods having bimodal locomotion, namely swimming and walking.

The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model.

BACKGROUND: Interactions between the sympathetic and somatic nervous system play an essential role in the pathophysiologic mechanisms of neuropathic pain. The α2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Multidrug therapy is potentially valuable to decrease side effects. OBJECTIVE: The aim of the present study was to investigate the possible antinociceptive effect of dexmedetomidine, an α2-adrenoceptor agonist, and its combination with front-line treatment of neuropathic pain, i.e., amitriptyline or tramadol, in a chronic constriction injury (CCI) model of the sciatic nerve in rats. STUDY DESIGN: Controlled animal study. METHODS: Following unilateral ligation of the left sciatic nerve, the effect of intraperitoneal (i.p.) dexmedetomidine (5 ug/kg), tramadol (5 mg/kg), and amitriptyline (30 mg/kg) on mechanical allodynia (measured by electrical von Frey apparatus) and hyperalgesia (measured by Randall and Selitto test) was studied. RESULTS: The sham-operated rats and un-operated hind paw (right paw) press normally on the floor reproduced by a weighted pain score of 0. Behavioral and mechanical tests confirmed the development of neuropathic pain after CCI. All individual drugs and dexmedetomidine combination with either tramadol or amitriptyline were effective in reducing mechanical allodynia and hyperalgesia. Dexmedetomidine, amitriptyline, tramadol, amitriptyline+dexmedetomidine, and tramadol+dexmedetomidine combination did not produce any sedation/motor impairment (P > 0.05). LIMITATIONS: Although the combination of these drugs improved the CCI model of neuropathic pain in this study, an additional interpretation of the underlying mechanism(s) will be needed to confirm these findings. CONCLUSION: The combination of these drugs appears to be more effective in increasing the pain threshold after peripheral nerve injury, when compared with the administration of either of amitriptyline or tramadol alone and should be considered as a possible alternative to decrease side effects of individual drug therapy.

Neurogenesis and growth factors expression after complete spinal cord transection in Pleurodeles waltlii.

Following spinal lesion, connections between the supra-spinal centers and spinal neuronal networks can be disturbed, which causes the deterioration or even the complete absence of sublesional locomotor activity. In mammals, possibilities of locomotion restoration are much reduced since descending tracts either have very poor regenerative ability or do not regenerate at all. However, in lower vertebrates, there is spontaneous locomotion recuperation after complete spinal cord transection at the mid-trunk level. This phenomenon depends on a translesional descending axon re-growth originating from the brainstem. On the other hand, cellular and molecular mechanisms underlying spinal cord regeneration and in parallel, locomotion restoration of the animal, are not well known. Fibroblast growth factor 2 (FGF-2) plays an important role in different processes such as neural induction, neuronal progenitor proliferation and their differentiation. Studies had shown an over expression of this growth factor after tail amputation. Nestin, a protein specific for intermediate filaments, is considered an early marker for neuronal precursors. It has been recently shown that its expression increases after tail transection in urodeles. Using this marker and western blots, our results show that the number of FGF-2 and FGFR2 mRNAs increases and is correlated with an increase in neurogenesis especially in the central canal lining cells immediately after lesion. This study also confirms that spinal cord re-growth through the lesion site initially follows a rostrocaudal direction. In addition to its role known in neuronal differentiation, FGF-2 could be implicated in the differentiation of ependymal cells into neuronal progenitors.

Fgf-2 in astroglial cells during vertebrate spinal cord recovery.

Fibroblast growth factor-2 is a pleiotrophic cytokine with neurotrophic and gliogenic properties. It is known to regulate CNS injury responses, which include transformation of reactive astrocytes, neurogenesis, and promotion of neurotrophic activities. In the brain, it is localized in astrocytes and discrete neuronal populations. Following both central and peripheral nervous system injury, astrocytes become reactive. These activated cells undergo hypertrophy. A key indicator of astrocyte activation is the increased accumulation of intermediate filaments composed of glial fibrillary acidic protein (GFAP). Following physical insult of brain or spinal cord, reactive astrocytes show increased FGF-2 immunoreactivity. Thus, FGF-2 appears to participate in astrocytic differentiation and proliferation and a good candidate for astrocytic function regulation in healthy, injured, or diseased CNS. To further investigate the cellular mechanisms underlying FGF-2 restorative actions and to analyze the changes within astroglial cells, we studied the localization of GFAP and FGF-2 in adult intact and injured Pleurodeles CNS. Our results show that spinal cord injury triggers a significant increase in FGF-2 immunoreactivity in reactive astrocytes at sites of insult. In addition, these results were time-dependent. Increase in FGF-2 immunoreactivity along the CNS axis, starting 1-week post-injury, was long-lasting extending to 6 weeks. This increase was accompanied by an increase in GFAP immunoreactivity in the same spatial pattern except in SC3 where its level was almost similar to sham-operated animals. Therefore, we suggest that FGF-2 may be involved in cell proliferation and/or astroglial cells differentiation after body spinal cord transection, and could thus play an important role in locomotion recovery.

Ectodermal FGFs induce perinodular inhibition of limb chondrogenesis in vitro and in vivo via FGF receptor 2.

The formation of cartilage elements in the developing vertebrate limb, where they serve as primordia for the appendicular skeleton, is preceded by the appearance of discrete cellular condensations. Control of the size and spacing of these condensations is a key aspect of skeletal pattern formation. Limb bud cell cultures grown in the absence of ectoderm formed continuous sheet-like masses of cartilage. With the inclusion of ectoderm, these cultures produced one or more cartilage nodules surrounded by zones of noncartilaginous mesenchyme. Ectodermal fibroblast growth factors (FGF2 and FGF8), but not a mesodermal FGF (FGF7), substituted for ectoderm in inhibiting chondrogenic gene expression, with some combinations of the two ectodermal factors leading to well-spaced cartilage nodules of relatively uniform size. Treatment of cultures with SU5402, an inhibitor FGF receptor tyrosine kinase activity, rendered FGFs ineffective in inducing perinodular inhibition. Inhibition of production of FGF receptor 2 (FGFR2) by transfection of wing and leg cell cultures with antisense oligodeoxynucleotides blocked appearance of ectoderm- or FGF-induced zones of perinodular inhibition of chondrogenesis and, when introduced into the limb buds of developing embryos, led to shorter, thicker, and fused cartilage elements. Because FGFR2 is expressed mainly at sites of precartilage condensation during limb development in vivo and in vitro, these results suggest that activation of FGFR2 by FGFs during development elicits a lateral inhibitor of chondrogenesis that limits the expansion of developing skeletal elements.