Accumulating evidence highlights chemokines as key mediators of the bidirectional crosstalk between neurons and glial cells aimed at preserving brain functioning. The multifaceted role of these immune proteins in the CNS is mirrored by the complexity of the mechanisms underlying its biological function, including biased signaling. Neurons, only in concert with glial cells, are essential players in the modulation of brain homeostatic functions. Yet, attempts to dissect these complex multilevel mechanisms underlying coordination are still lacking. Therefore, the purpose of this review is to summarize the current knowledge about mechanisms underlying chemokine regulation of neuron–glia crosstalk linking molecular, cellular, network, and behavioral levels. Following a brief description of molecular mechanisms by which chemokines interact with their receptors and then summarizing cellular patterns of chemokine expression in the CNS, we next delve into the sequence and mechanisms of chemokine-regulated neuron–glia communication in the context of neuroprotection. We then define the interactions with other neurotransmitters, neuromodulators, and gliotransmitters. Finally, we describe their fine-tuning on the network level and the behavioral relevance of their modulation. We believe that a better understanding of the sequence and nature of events that drive neuro-glial communication holds promise for the development of new treatment strategies that could, in a context- and time-dependent manner, modulate the action of specific chemokines to promote brain repair and reduce the neurological impairment.

Theta oscillations generated in hippocampal (HPC) and cortical neuronal networks are involved in various aspects of brain function, including sensorimotor integration, movement planning, memory formation and attention. Disruptions of theta rhythms are present in individuals with brain disorders, including epilepsy and Alzheimer’s disease. Theta rhythm generation involves a specific interplay between cellular (ion channel) and network (synaptic) mechanisms. HCN channels are theta modulators, and several medications are known to enhance their activity. We investigated how different doses of lamotrigine (LTG), an HCN channel modulator, and antiepileptic and neuroprotective agent, would affect HPC theta rhythms in acute HPC slices (in vitro) and anaesthetized rats (in vivo). Whole-cell patch clamp recordings revealed that LTG decreased GABA_A-fast transmission in CA3 cells, in vitro. In addition, LTG directly depressed CA3 and CA1 pyramidal neuron excitability. These effects were partially blocked by ZD 7288, a selective HCN blocker, and are consistent with decreased excitability associated with antiepileptic actions. Lamotrigine depressed HPC theta oscillations in vitro, also consistent with its neuronal depressant effects. In contrast, it exerted an opposite, enhancing effect, on theta recorded in vivo. The contradictory in vivo and in vitro results indicate that LTG increases ascending theta activating medial septum/entorhinal synaptic inputs that over-power the depressant effects seen in HPC neurons. These results provide new insights into LTG actions and indicate an opportunity to develop more precise therapeutics for the treatment of dementias, memory disorders and epilepsy.

It has been hypothesized that efficient reading is possible because all reading scripts have been matched, through cultural evolution, to the natural capabilities of the visual cortex. This matching has resulted in all scripts being made of line-junctions, such as T, X or L. Our aim was to test a critical prediction of this hypothesis: visual reading in an atypical script that is devoid of line-junctions (such as the Braille alphabet read visually) should be much less efficient than reading in a “normal” script (e.g., Cyrillic). Using a lexical decision task, we examined Visual Braille reading speed and efficiency in sighted Braille teachers. As a control, we tested learners of a natural visual script, Cyrillic. Both groups participated in a two semester course of either visual Braille or Russian while their reading speed and accuracy was tested at regular intervals. The results show that visual Braille reading is slow, prone to errors and highly serial, even in Braille readers with years of prior reading experience. Although subjects showed some improvements in their visual Braille reading accuracy and speed following the course, the effect of word length on reading speed (typically observed in beginning readers) was remained very sizeable through all testing sessions. These results are in stark contrast to Cyrillic, a natural script, where only three months of learning were sufficient to achieve relative proficiency. Taken together, these results suggest that visual features such as line junctions and their combinations might be necessary for efficient reading.

Rationale Chronic stress and corticosterone have been shown to affect serotonin (5-HT) neurotransmission; however, the influence of stress on the activity of the dorsal raphe nucleus (DRN), the main source of 5-HT in the forebrain, is not well understood. In particular, it is unknown if and how stress modifies DRN 5-HT₇ receptors, which are involved in the modulation of the firing of local inhibitory interneurons responsible for regulating the activity of DRN projection cells. Objectives Our study aimed to investigate the effect of repeated corticosterone injections on the modulation of the inhibitory transmission within the DRN by 5-HT₇ receptors and whether it could be reversed by treatment with a 5-HT₇ receptor antagonist. Methods Male Wistar rats received corticosterone injections repeated twice daily for 14 days. Spontaneous inhibitory postsynaptic currents (sIPSCs) were then recorded from DRN projection cells in ex vivo slice preparations obtained 24 h after the last injection. Results Repeated corticosterone administration resulted in decreased frequency, but not amplitude, of sIPSCs in DRN projection cells. There were no changes in the excitability of these cells; however, corticosterone treatment suppressed the 5-HT₇ receptor-mediated increase in sIPSC frequency. Administration of the 5-HT₇ receptor antagonist SB 269970 for 7 days beginning on the eighth day of corticosterone treatment reversed the detrimental effects of corticosterone on 5-HT₇ receptor reactivity and GABAergic transmission in the DRN. Conclusions Elevated corticosterone level reduces DRN 5HT₇ receptor reactivity and decreases GABAergic transmission within the DRN, which can be reversed by the 5-HT₇ receptor antagonist SB 269970.