Updated November 12th, 2024
Research Spotlight
Transgenic mouse lines that allow selective control of specific neuronal populations have been key to expanding the understanding of central amygdala microcircuitry, and the functional role of PKCδ-expressing neurons. However, within several behavioral domains, such as social behaviors and drug-seeking- and taking, availability of rat models importantly expands research opportunities. Toivainen, Petrella, and colleagues generated and characterized a novel PKCδ-Cre knock-in rat model that offers novel opportunities for functional studies of PKCδ-expressing neurons in behaviors relevant to human conditions.
Synapses are essential for brain communication and disruption of synapses are linked to various brain disorders. Johansen, Beliveau, and colleagues present a detailed in vivo 3D atlas of synapses in the human brain using advanced neuroimaging techniques which are calibrated to absolute density values. This groundbreaking map shows how synapse density varies across different brain regions and how these variations relate to brain function. The study also discovered that people with higher IQs tend to have more synapses in certain brain areas. This new human brain atlas will help scientists better understand brain function and can lead to new insights into brain disorders.
Alzheimer’s disease (AD) is characterized, in part, by the buildup of amyloid plaques, which may be worsened by a particular gene that facilitates amyloid pathology. A mutation of this gene—the Icelandic mutation—may protect against AD pathology ex vivo, supporting the idea that inducing the mutation in vivo could be an effective approach to AD treatment. However, whether the Icelandic mutation affects amyloid pathology in mammals in vivo has not been assessed until now. Hiroki Sasaguri from the RIKEN Center for Brain Science led a study using a genetic mouse model mimicking the amyloid pathology observed in humans with AD. Inducing the Icelandic mutation in these mice led to a reduction of amyloid plaques and other AD pathology. The researchers also uncovered a mechanism for the Icelandic mutation’s protective effects in mice. According to the authors, while in vivo genome editing was not used in this study, these findings support the idea that a genome editing treatment strategy has potential in mammals and thus may inform future studies.
The third trimester is crucial for the developing brain networks that support lifelong cognitive abilities, yet it is not well understood how this communication between brain regions develops during this period. In this study, Yrjölä and colleagues uncover the early development of human brain activity patterns from preterm-born infants and discuss their potential links to established neurophysiological processes. These findings provide developmental templates for future basic and clinical research.
Most-Discussed Research Published in October
Below are five Early Release articles that generated the most online discussion in October 2024, as measured by Altmetric. Altmetric data is available for all articles published in JNeurosci on the Info & Metrics tab. Learn more about how the Altmetric score is calculated.
The spatiotemporal dynamics of bottom-up and top-down processing during at-a-glance reading
Language processing, like all cognitive domains, is profoundly influenced by top-down knowledge. One type of evidence of this is oversight of errors in the signal. For example, in sentence comprehension, individuals often fail to detect word order errors, such as transposed words mid-sentence. Utilizing rapid parallel visual presentation (RPVP), we investigated this phenomenon by exposing participants to four-word sentences for 300ms. Magnetoencephalography revealed robust differentiation between grammatical and reversed sentences in left lateral language cortex starting at 213ms post-presentation. Intriguingly, initial neural responses to inner transpositions treated them as deviant, but 100ms later, neural signals grouped them with grammatical sentence, indicating rapid error correction. These findings reveal the brain's remarkable capacity to reconcile bottom-up input with linguistic knowledge almost instantaneously.
Neural predictors of fear depend on the situation
Much of the debate on the nature of emotion concerns the uniformity or heterogeneity of representation for particular emotion categories. Here we provide evidence that widely distributed activation patterns characteristic of recent neural signatures of fear reflect an amalgam of functionally heterogeneous brain states. Participants completed a novel fMRI task that parametrically examined subjective fear within and across three content-rich and naturalistic situations: fear of heights, spiders, and social threats. Using searchlight analysis and machine learning methods, we show that the overwhelming majority of brain regions that predict fear only do so for certain situations. These findings carry implications for the generalization of findings on fear across species, translational models of fear and anxiety, and developing neural signatures of fear.
We show here the mechanisms and role of astrocytes and gliotransmitters in a postsynaptic spike timing dependent long-term depression (t-LTD) form defined at layer (L)2/3-L2/3 synapses of the somatosensory cortex. We have discovered that this form of plasticity involves N-methyl D-aspartate receptors (NMDAR) containing the GluN2B subunit and requires astrocytes and the gliotransmitter D-serine to co-activate (together with glutamate) postsynaptic NMDAR to mediate LTD. This can be a general mechanism in the brain to define different forms of plasticity. Defining the mechanisms of synaptic plasticity may have important implications for brain repair, sensorial recovery, the treatment of neurodevelopmental disorders and even, for educational policy.
Orbitofrontal cortex mediates sustained basolateral amygdala encoding of cued reward seeking states
Appropriate representation of the current need for motivated reward seeking, especially under situations of uncertainty or ambiguity, is critical for adaptive behavior. Here, we recorded activity of neurons in the basolateral amygdala (BLA) in rats during conditioned reward seeking, finding a sustained cue-evoked population-level code, which terminated once reward was received. Inactivation of a major BLA input, the orbitofrontal cortex (OFC), blunted sustained cue-evoked activity in BLA and reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in BLA also reduced reward seeking. Together, these results show that the BLA represents conditioned motivational states with sustained neural activity - this signal is critical for cue-invigorated reward seeking and depends on functional input from the orbitofrontal cortex.
Monocyte invasion into the retina restricts the regeneration of neurons from Müller glia
Regeneration of neurons in the central nervous system is extremely limited in mammals. Transgenic overexpression of the proneural transcription factor Ascl1 enables mammalian retinal glia to regenerate some neurons lost to injury. We found that during this regenerative response to injury, monocytes from the periphery invade the neural retina and these inflammatory cells negatively regulate the ability of Müller glia to reprogram into neurogenic progenitors. When monocytes are inhibited from infiltrating the retina, regeneration of neurons from Müller glia is significantly enhanced. This work implicates peripheral immunomodulation as a tool to enhance endogenous neuronal replacement strategies.
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