Current research in neurobiology最新文献

A fundamental problem in neuroscience is how neurons select for their many inputs. A common assumption is that a neuron's selectivity is largely explained by differences in excitatory synaptic input weightings. Here we describe another solution to this important problem. We show that within the first order visual thalamus, the type of inhibition provided by thalamic interneurons has the potential to alter the input selectivity of thalamocortical neurons. To do this, we developed conductance injection protocols to compare how different types of synchronous and asynchronous GABA release influence thalamocortical excitability in response to realistic patterns of retinal ganglion cell input. We show that the asynchronous GABA release associated with tonic inhibition is particularly efficient at maintaining information content, ensuring that thalamocortical neurons can distinguish between their inputs. We propose a model where alterations in GABA release properties results in rapid changes in input selectivity without requiring structural changes in the network.

Parvalbumin-expressing (PV+) inhibitory interneurons drive gamma oscillations (30–80 Hz), which underlie higher cognitive functions. In this review, we discuss two groups/aspects of fundamental properties of PV+ interneurons. In the first group (dubbed Before Axon), we list properties representing optimal synaptic integration in PV+ interneurons designed to support fast oscillations. For example: [i] Information can neither enter nor leave the neocortex without the engagement of fast PV+ -mediated inhibition; [ii] Voltage responses in PV+ interneuron dendrites integrate linearly to reduce impact of the fluctuations in the afferent drive; and [iii] Reversed somatodendritic Rm gradient accelerates the time courses of synaptic potentials arriving at the soma. In the second group (dubbed After Axon), we list morphological and biophysical properties responsible for (a) short synaptic delays, and (b) efficient postsynaptic outcomes. For example: [i] Fast-spiking ability that allows PV+ interneurons to outpace other cortical neurons (pyramidal neurons). [ii] Myelinated axon (which is only found in the PV+ subclass of interneurons) to secure fast-spiking at the initial axon segment; and [iii] Inhibitory autapses – autoinhibition, which assures brief biphasic voltage transients and supports postinhibitory rebounds. Recent advent of scientific tools, such as viral strategies to target PV cells and the ability to monitor PV cells via in vivo imaging during behavior, will aid in defining the role of PV cells in the CNS. Given the link between PV+ interneurons and cognition, in the future, it would be useful to carry out physiological recordings in the PV+ cell type selectively and characterize if and how psychiatric and neurological diseases affect initiation and propagation of electrical signals in this cortical sub-circuit. Voltage imaging may allow fast recordings of electrical signals from many PV+ interneurons simultaneously.

We argue that prediction success maximization is a basic objective of cognition and cortex, that it is compatible with but distinct from prediction error minimization, that neither objective requires subtractive coding, that there is clear neurobiological evidence for the amplification of predicted signals, and that we are unconvinced by evidence proposed in support of subtractive coding. We outline recent discoveries showing that pyramidal cells on which our cognitive capabilities depend usually transmit information about input to their basal dendrites and amplify that transmission when input to their distal apical dendrites provides a context that agrees with the feedforward basal input in that both are depolarizing, i.e., both are excitatory rather than inhibitory. Though these intracellular discoveries require a level of technical expertise that is beyond the current abilities of most neuroscience labs, they are not controversial and acclaimed as groundbreaking. We note that this cellular cooperative context-sensitivity greatly enhances the cognitive capabilities of the mammalian neocortex, and that much remains to be discovered concerning its evolution, development, and pathology.

The endosomal sorting complexes required for transport (ESCRT) pathway is composed of a series of protein complexes that are essential for sorting cargo through the endosome. In neurons, the ESCRT pathway is a key mediator of many cellular pathways that regulate neuronal morphogenesis as well as synaptic growth and function. The ESCRT-0 complex, consisting of HGS (hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (signal-transducing adaptor molecule), acts as a gate keeper to this pathway, ultimately determining the fate of the endosomal cargo. We previously showed that a single nucleotide substitution in Hgs results in structural and functional changes in the nervous system of teetering mice. To determine if these changes occurred as a function of HGS's role in the ESCRT pathway and its association with STAM1, we investigated if STAM1 deficiency also leads to a similar impairment of the nervous system. In contrast to teetering mice that die within 5 weeks of age and exhibit reduced body mass, 1-month-old Stam1 knockout mice were not visibly different from controls. However, by 3 months of age, STAM1 deficiency caused reduced muscle mass, strength, and motor performance. These changes in motor function did not correlate with either a loss in motor neuron number or abnormal myelination of peripheral nerves. Instead, the motor endplate structure was altered in the Stam1 knockout mice by 1 month of age and continued to degenerate over time, correlating with a significant reduction in muscle fiber size and increased expression of the embryonic γ acetylcholine receptor (AChR) subunit at 3 months of age. There was also a significant reduction in the levels of two presynaptic SNARE proteins, VTI1A and VAMP2, in the motor neurons of the Stam1 knockout mice. As loss of STAM1 expression replicates many of the structural changes at the motor endplates that we have previously reported with loss of HGS, these results suggest that the HGS/STAM1 complex plays a critical role in maintaining synaptic structure and function in the mammalian nervous system.

The human voice is a critical stimulus for the auditory system that promotes social connection, informs the listener about identity and emotion, and acts as the carrier for spoken language. Research on voice processing in adults has informed our understanding of the unique status of the human voice in the mature auditory cortex and provided potential explanations for mechanisms that underly voice selectivity and identity processing. There is evidence that voice perception undergoes developmental change starting in infancy and extending through early adolescence. While even young infants recognize the voice of their mother, there is an apparent protracted course of development to reach adult-like selectivity for human voice over other sound categories and recognition of other talkers by voice. Gaps in the literature do not allow for an exact mapping of this trajectory or an adequate description of how voice processing and its neural underpinnings abilities evolve. This review provides a comprehensive account of developmental voice processing research published to date and discusses how this evidence fits with and contributes to current theoretical models proposed in the adult literature. We discuss how factors such as cognitive development, neural plasticity, perceptual narrowing, and language acquisition may contribute to the development of voice processing and its investigation in children. We also review evidence of voice processing abilities in premature birth, autism spectrum disorder, and phonagnosia to examine where and how deviations from the typical trajectory of development may manifest.

Accurate sound perception can require integrating information over hundreds of milliseconds or even seconds. Spectro-temporal models of sound coding by single neurons in auditory cortex indicate that the majority of sound-evoked activity can be attributed to stimuli with a few tens of milliseconds. It remains uncertain how the auditory system integrates information about sensory context on a longer timescale. Here we characterized long-lasting contextual effects in auditory cortex (AC) using a diverse set of natural sound stimuli. We measured context effects as the difference in a neuron's response to a single probe sound following two different context sounds. Many AC neurons showed context effects lasting longer than the temporal window of a traditional spectro-temporal receptive field. The duration and magnitude of context effects varied substantially across neurons and stimuli. This diversity of context effects formed a sparse code across the neural population that encoded a wider range of contexts than any constituent neuron. Encoding model analysis indicates that context effects can be explained by activity in the local neural population, suggesting that recurrent local circuits support a long-lasting representation of sensory context in auditory cortex.

The canonical Wnt signaling is an essential pathway that regulates cellular proliferation, maturation, and differentiation during neurodevelopment and maintenance of adult tissue homeostasis. This pathway has been implicated with the pathophysiology of neuropsychiatric disorders and was associated with cognitive processes, such as learning and memory. However, the molecular investigation of the Wnt signaling in functional human neural cell lines might be challenging since brain biopsies are not possible and animal models may not represent the polygenic profile of some neurological and neurodevelopmental disorders. In this context, using induced pluripotent stem cells (iPSCs) has become a powerful tool to model disorders that affect the Central Nervous System (CNS) in vitro, by maintaining patients’ genetic backgrounds. In this method paper, we report the development of a virus-free Wnt reporter assay in neural stem cells (NSCs) derived from human iPSCs from two healthy individuals, by using a vector containing a reporter gene (luc2P) under the control of a TCF/LEF (T-cell factor/lymphoid enhancer factor) responsive element. Dose-response curve analysis from this luciferase-based method might be useful when testing the activity of the Wnt signaling pathway after agonists (e.g. Wnt3a) or antagonists (e.g. DKK1) administration, comparing activity between cases and controls in distinct disorders. Using such a reporter assay method may help to elucidate whether neurological or neurodevelopmental mental disorders show alterations in this pathway, and testing whether targeted treatment may reverse these. Therefore, our established assay aims to help researchers on the functional and molecular investigation of the Wnt pathway in patient-specific cell types comprising several neuropsychiatric disorders.

A view continues to gain momentum that regards investigation of the cognition of great apes in captive settings as affording us a model for human cognitive evolution. Researchers from disciplines such as comparative psychology, anthropology, and even archaeology, seem eager to put their theories to the test by using great apes as their chosen experimental model. Questions addressed currently by comparative psychologists have long been the object of attention by neurophysiologists, psychobiologists and neuroscientists, who, however, often use rodents and monkeys as the species of choice. Whereas comparative psychology has been influenced greatly by ethology, much neuroscience has developed against a background of physiology and medicine. This separation of the intellectual contexts wherein they have arisen and flourished has impeded the development of fluid interaction between comparative psychologists and researchers in the other disciplines. We feel that it would be beneficial for comparative psychologists and neuroscientists to combine research endeavours far more often, in order to address common questions of interest related to cognition. We regard interdisciplinary cross-pollination to be particularly desirable, even if many comparative psychologists lack deep expertise about the workings of the brain, and even if many neuroscientists lack expert knowledge about the behaviour of different species. Furthermore, we believe that anthropology, archaeology, human evolutionary studies, and related disciplines, may well provide us with significant contextual knowledge about the physical and temporal background to the evolution in humans of specific cognitive skills. To that end, we urge researchers to dismantle methodological, conceptual and historical disciplinary boundaries, in order to strengthen cross-disciplinary cooperation in order to broaden and deepen our insights into the cognition of nonhuman and human primates.