GABAergic inhibition is an important regulator of excitability in neuronal networks. In addition, inhibitory synaptic signals contribute crucially to the organization of spatiotemporal patterns of network activity, especially during coherent oscillations. In order to maintain stable network states, the release of GABA by interneurons must be plastic in timing and amount. This homeostatic regulation is achieved by several pre- and postsynaptic mechanisms and is triggered by various activity-dependent local signals such as excitatory input or ambient levels of neurotransmitters. Here, we review findings on the availability of GABA for release at presynaptic terminals of interneurons. Presynaptic GABA content seems to be an important determinant of inhibitory efficacy and can be differentially regulated by changing synthesis, transport, and degradation of GABA or related molecules. We will discuss the functional impact of such regulations on neuronal network patterns and, finally, point towards pharmacological approaches targeting these processes.

Neurons form transiently stable assemblies that may underlie cognitive functions, including memory formation. In most brain regions, coherent activity is organized by network oscillations that involve sparse firing within a well-defined minority of cells. Despite extensive work on the underlying cellular mechanisms, a fundamental question remains unsolved: how are participating neurons distinguished from the majority of nonparticipators? We used physiological and modeling techniques to analyze neuronal activity in mouse hippocampal slices during spontaneously occurring high-frequency network oscillations. Network-entrained action potentials were exclusively observed in a defined subset of pyramidal cells, yielding a strict distinction between participating and nonparticipating neurons. These spikes had unique properties, because they were generated in the axon without prior depolarization of the soma. GABA _A receptors had a dual role in pyramidal cell recruitment. First, the sparse occurrence of entrained spikes was accomplished by intense perisomatic inhibition. Second, antidromic spike generation was facilitated by tonic effects of GABA in remote axonal compartments. Ectopic spike generation together with strong somatodendritic inhibition may provide a cellular mechanism for the definition of oscillating assemblies.

Amyloid precursor protein (APP) is critically involved in the pathophysiology of Alzheimer’s disease, but its physiological functions remain elusive. Importantly, APP knockout (APP-KO) mice exhibit cognitive deficits, suggesting that APP plays a role at the neuronal network level. To investigate this possibility, we recorded local field potentials (LFPs) from the posterior parietal cortex, dorsal hippocampus and lateral prefrontal cortex of freely moving APP-KO mice. Spectral analyses showed that network oscillations within the theta- and gamma-frequency bands were not different between APP-KO and wild-type mice. Surprisingly, however, while gamma amplitude coupled to theta phase in all recorded regions of wild-type animals, in APP-KO mice theta-gamma coupling was strongly diminished in recordings from the parietal cortex and hippocampus, but not in LFPs recorded from the prefrontal cortex. Thus, lack of APP reduces oscillatory coupling in LFP recordings from specific brain regions, despite not affecting the amplitude of the oscillations. Together, our findings reveal reduced cross-frequency coupling as a functional marker of APP deficiency at the network level.

Despite its key role in the molecular pathology of Alzheimer’s disease (AD), the physiological function of Amyloid Precursor Protein (APP) is unknown. Increasing evidence, however, points towards a neuroprotective role of this membrane protein in situations of metabolic stress. A key observation is the up-regulation of APP following acute (stroke, cardiac arrest) or chronic (cerebrovascular disease) hypoxic-ischemic conditions. While this mechanism may increase the risk or severity of AD, APP by itself or its soluble extracellular fragment APPsα can promote neuronal survival. Indeed, different animal models of acute hypoxia-ischemia, traumatic brain injury (TBI) and excitotoxicity have revealed protective effects of APP or APPsα. The underlying mechanisms involve APP-mediated regulation of calcium homeostasis via NMDA receptors, voltage-gated calcium channels (VGCC) or internal calcium stores. In addition, APP affects the expression of survival- or apoptosis- related genes as well as neurotrophic factors. In this review, we summarize the current understanding of the neuroprotective role of APP and APPs and possible implications for future research and new therapeutic strategies.

Claims that plants have conscious experiences have increased in recent years and have received wide coverage, from the popular media to scientific journals. Such claims are misleading and have the potential to misdirect funding and governmental policy decisions. After defining basic, primary consciousness, we provide new arguments against 12 core claims made by the proponents of plant consciousness. Three important new conclusions of our study are (1) plants have not been shown to perform the proactive, anticipatory behaviors associated with consciousness, but only to sense and follow stimulus trails reactively; (2) electrophysiological signaling in plants serves immediate physiological functions rather than integrative-information processing as in nervous systems of animals, giving no indication of plant consciousness; (3) the controversial claim of classical Pavlovian learning in plants, even if correct, is irrelevant because this type of learning does not require consciousness. Finally, we present our own hypothesis, based on two logical assumptions, concerning which organisms possess consciousness. Our first assumption is that affective (emotional) consciousness is marked by an advanced capacity for operant learning about rewards and punishments. Our second assumption is that image-based conscious experience is marked by demonstrably mapped representations of the external environment within the body. Certain animals fit both of these criteria, but plants fit neither. We conclude that claims for plant consciousness are highly speculative and lack sound scientific support.