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Corticothalamic circuits are essential for reciprocal information exchange between the thalamus and cerebral cortex. Nevertheless, the role of corticothalamic circuits in sensory processing remains a mystery. In the visual system, afferents from retina to the lateral geniculate nucleus (LGN) and from LGN to primary visual cortex (V1) are organized into functionally distinct parallel processing streams...
Properly functional CNS circuits depend on inhibitory interneurons that in turn rely upon activity-dependent gene expression for morphological development, connectivity, and excitatory-inhibitory coordination. Despite its importance, excitation-transcription coupling in inhibitory interneurons is poorly understood. We report that PV+ interneurons employ a novel CaMK-dependent pathway to trigger CREB...
Changes in neuronal activity create local and transient changes in energy demands at synapses. Here we discover a metabolic compartment that forms in vivo near synapses to meet local energy demands and support synaptic function in Caenorhabditis elegans neurons. Under conditions of energy stress, glycolytic enzymes redistribute from a diffuse localization in the cytoplasm to a punctate localization...
Electrical and chemical synapses coexist in circuits throughout the CNS. Yet, it is not well understood how electrical and chemical synaptic transmission interact to determine the functional output of networks endowed with both types of synapse. We found that release of glutamate from bipolar cells onto retinal ganglion cells (RGCs) was strongly shaped by gap-junction-mediated electrical coupling...
While transcriptional controls over the size and relative position of cortical areas have been identified, less is known about regulators that direct acquisition of area-specific characteristics. Here, we report that the transcription factor Ctip1 functions in primary sensory areas to repress motor and activate sensory programs of gene expression, enabling establishment of sharp molecular boundaries...
Tau toxicity has been implicated in the emergence of synaptic dysfunction in Alzheimer’s disease (AD), but the mechanism by which tau alters synapse physiology and leads to cognitive decline is unclear. Here we report abnormal acetylation of K274 and K281 on tau, identified in AD brains, promotes memory loss and disrupts synaptic plasticity by reducing postsynaptic KIdney/BRAin (KIBRA) protein, a...
For goal-directed action to remain adaptive, new strategies are required to accommodate environmental changes, a process for which parafascicular thalamic modulation of cholinergic interneurons in the striatum (PF-to-CIN) appears critical. In the elderly, however, previously acquired experience frequently interferes with new learning, yet the source of this effect has remained unexplored. Here, combining...
In daylight, the input to the retinal circuit is provided primarily by cone photoreceptors acting as band-pass filters, but the retinal output also contains neuronal populations transmitting sustained signals. Using in vivo imaging of genetically encoded calcium reporters, we investigated the circuits that generate these sustained channels within the inner retina of zebrafish. In OFF bipolar cells,...
Sniffing and whisking typify the exploratory behavior of rodents. These actions involve separate oscillators in the medulla, located respectively in the pre-Bötzinger complex (preBötC) and the vibrissa-related region of the intermediate reticular formation (vIRt). We examine how these oscillators synergize to control sniffing and whisking. We find that the vIRt contains glycinergic/GABAergic cells...
The basolateral amygdala (BLA) is critical for encoding the value of stimuli. Beyeler et al. (2016) now show that distinct populations of BLA neurons, which are defined by their efferent targets, code reward and aversion. This arrangement promotes parallel processing of biologically relevant events.
Recently it was proposed that the familial Alzheimer’s disease (FAD) causing presenilin (PSEN) mutations PSEN1-L435F and PSEN1-C410Y do not support the generation of Aβ-peptides from the amyloid precursor protein (APP). This challenges the amyloid hypothesis and disagrees with previous work showing that PSEN1 FAD causing mutations generate invariably long Aβ and seed amyloid. We contrast here the...
In this issue of Neuron, Kuo et al. (2016) show that coordinated interaction between electrical and chemical synapses in a defined retinal circuit enhances sensitivity to moving objects. Their work demonstrates how electrical and chemical synapses combine to improve information processing in a specific area of the CNS.
By using a tau construct with two mimicked acetylation sites as identified in AD brains, Tracy et al. (2016) found that acetylated tau promotes synaptic dysfunction through disruption of postsynaptic KIBRA signaling pathways, actin dynamics, and AMPA receptor trafficking.
In this issue of Neuron, Deschênes et al. (2016) propose that rhythmic inhibition of whisker motor neurons is a key pattern generator underlying exploratory whisking. The inhibitory premotor neurons located in the brainstem reticular formation are synchronized by breathing-related oscillators.
Sophisticated video games that integrate engaging cognitive training with real-time biosensing and neurostimulation have the potential to optimize cognitive performance in health and disease. We argue that technology development must be paired with rigorous scientific validation and discuss academic and industry opportunities in this field.
The mesopontine tegmentum, including the pedunculopontine and laterodorsal tegmental nuclei (PPN and LDT), provides major cholinergic inputs to midbrain and regulates locomotion and reward. To delineate the underlying projection-specific circuit mechanisms, we employed optogenetics to control mesopontine cholinergic neurons at somata and at divergent projections within distinct midbrain areas. Bidirectional...
The common marmoset (Callithrix jacchus) has garnered interest recently as a powerful model for the future of neuroscience research. Much of this excitement has centered on the species’ reproductive biology and compatibility with gene editing techniques, which together have provided a path for transgenic marmosets to contribute to the study of disease as well as basic brain mechanisms. In step with...
Although the basolateral amygdala (BLA) is known to play a critical role in the formation of memories of both positive and negative valence, the coding and routing of valence-related information is poorly understood. Here, we recorded BLA neurons during the retrieval of associative memories and used optogenetic-mediated phototagging to identify populations of neurons that synapse in the nucleus accumbens...
Humans and monkeys have access to an accurate representation of visual space despite a constantly moving eye. One mechanism by which the brain accomplishes this is by remapping visual receptive fields around the time of a saccade. In this process a neuron can be excited by a probe stimulus in the current receptive field, and also simultaneously by a probe stimulus in the location that will be brought...
We recently reported that homozygous Presenilin-1 (Psen1) knockin (KI) mice carrying the familial Alzheimer’s disease (FAD) mutation L435F or C410Y recapitulate the phenotypes of Psen1−/− mice. Production and steady-state levels of Aβ40 and Aβ42 are undetectable in KI/KI brains and reduced in KI/+ brains, though the Aβ42/Aβ40 ratio is slightly increased in KI/+ brains. Moreover, the FAD mutation impairs...
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