Astrocytes enhance plasticity response during reversal learning.

Astrocytes play a key role in the regulation of synaptic strength and are thought to orchestrate synaptic plasticity and memory. Yet, how specifically astrocytes and their neuroactive transmitters control learning and memory is currently an open question. Recent experiments have uncovered an astrocyte-mediated feedback loop in CA1 pyramidal neurons which is started by the release of endocannabinoids by active neurons and closed by astrocytic regulation of the D-serine levels at the dendrites.

Activity-induced reactivity of astrocytes impairs cognition.

Glial cells such as astrocytes can modulate neuronal signaling. Astrocytes can also acquire a reactive phenotype that correlates with cognitive impairments in brain diseases. A study in PLOS Biology shows that prolonged activation of astrocytes can trigger both cognitive impairments and a reactive astrocyte phenotype.

Astrocytes as Drivers and Disruptors of Behavior: New Advances in Basic Mechanisms and Therapeutic Targeting.

Astrocytes are emerging as key regulators of cognitive function and behavior. This review highlights some of the latest advances in the understanding of astrocyte roles in different behavioral domains across lifespan and in disease. We address specific molecular and circuit mechanisms by which astrocytes modulate behavior, discuss their functional diversity and versatility, and highlight emerging astrocyte-targeted treatment strategies that might alleviate behavioral and cognitive dysfunction in pathologic conditions.

An astrocytic signaling loop for frequency-dependent control of dendritic integration and spatial learning.

Dendrites of hippocampal CA1 pyramidal cells amplify clustered glutamatergic input by activation of voltage-gated sodium channels and N-methyl-D-aspartate receptors (NMDARs). NMDAR activity depends on the presence of NMDAR co-agonists such as D-serine, but how co-agonists influence dendritic integration is not well understood. Using combinations of whole-cell patch clamp, iontophoretic glutamate application, two-photon excitation fluorescence microscopy and glutamate uncaging in acute rat and mouse brain slices we found that exogenous D-serine reduced the threshold of dendritic spikes and increased their amplitude.

Targeting aberrant dendritic integration to treat cognitive comorbidities of epilepsy.

Memory deficits are a debilitating symptom of epilepsy, but little is known about mechanisms underlying cognitive deficits. Here, we describe a Na+ channel-dependent mechanism underlying altered hippocampal dendritic integration, degraded place coding and deficits in spatial memory. Two-photon glutamate uncaging experiments revealed a marked increase in the fraction of hippocampal first-order CA1 pyramidal cell dendrites capable of generating dendritic spikes in the kainate model of chronic epilepsy.

Astrocytes in memory formation and maintenance.

Learning and memory are fundamental but highly complex functions of the brain. They rely on multiple mechanisms including the processing of sensory information, memory formation, maintenance of short- and long-term memory, memory retrieval and memory extinction. Recent experiments provide strong evidence that, besides neurons, astrocytes crucially contribute to these higher brain functions.

Local Resting Ca Controls the Scale of Astroglial Ca Signals.

Astroglia regulate neurovascular coupling while engaging in signal exchange with neurons. The underlying cellular machinery is thought to rely on astrocytic Ca signals, but what controls their amplitude and waveform is poorly understood. Here, we employ time-resolved two-photon excitation fluorescence imaging in acute hippocampal slices and in cortex in vivo to find that resting [Ca] predicts the scale (amplitude) and the maximum (peak) of astroglial Ca elevations.

Stress and Corticosteroids Aggravate Morphological Changes in the Dentate Gyrus after Early-Life Experimental Febrile Seizures in Mice.

Stress is the most frequently self-reported seizure precipitant in patients with epilepsy. Moreover, a relation between ear stress and epilepsy has been suggested. Although ear stress and stress hormones are known to influence seizure threshold in rodents, effects on the development of epilepsy (epileptogenesis) are still unclear.

The structural and functional evidence for vesicular release from astrocytes in situ.

The concept of the tripartite synapse states that bi-directional signalling between perisynaptic astrocyte processes, presynaptic axonal boutons and postsynaptic neuronal structures defines the properties of synaptic information processing. Ca-dependent vesicular release from astrocytes, as one of the mechanisms of astrocyte-neuron communication, has attracted particular attention but has also been the subject of intense debate. In neurons, regulated vesicular release is a strongly coordinated process.