Neuroscientist最新文献

Windows of plasticity are fundamental for the correct formation of definitive brain circuits; these periods drive sensory and motor learning during development and ultimately learning and memory in adults. However, establishing windows of plasticity also imposes limitations on the central nervous system in terms of its capacity to recover from injury. Recent evidence highlights the important role that astrocytes and adenosine seem to play in controlling the duration of these critical periods of plasticity.

Perineuronal nets (PNNs) are specialized structures of the extracellular matrix that surround the soma and proximal dendrites of certain neurons in the central nervous system, particularly parvalbumin-expressing interneurons. Their appearance overlaps the maturation of neuronal circuits and the closure of critical periods in different regions of the brain, setting their connectivity and abruptly reducing their plasticity. As a consequence, the digestion of PNNs, as well as the removal or manipulation of their components, leads to a boost in this plasticity and can play a key role in the functional recovery from different insults and in the etiopathology of certain neurologic and psychiatric disorders. Here we review the structure, composition, and distribution of PNNs and their variation throughout the evolutive scale. We also discuss methodological approaches to study these structures. The function of PNNs during neurodevelopment and adulthood is discussed, as well as the influence of intrinsic and extrinsic factors on these specialized regions of the extracellular matrix. Finally, we review current data on alterations in PNNs described in diseases of the central nervous system (CNS), focusing on psychiatric disorders. Together, all the data available point to the PNNs as a promising target to understand the physiology and pathologic conditions of the CNS.

History has conflated the legacies of José Manuel Rodríguez Delgado and Walter Freeman, midcentury proponents of somatic therapies for neuropsychiatric conditions. Both gained notoriety: Delgado after he appeared on the front page of the New York Times having used his stimoceiver to stop a charging bull in Spain; Freeman as the proponent of lobotomy. Both were the object of critique by the antipsychiatry movement and those who felt that their methods and objectives posed a threat to personal liberty. Using archival sources, we demonstrate that this conflation is a misrepresentation of the historical record and that their methods, objectives, ethics, and philosophical commitments differed widely. Accurate knowledge about historical antecedents is a predicate for ethical analysis and becomes especially relevant information as neuroscience develops circuit-based treatments for conditions such as Parkinson disease, depression, and brain injury. Part of that corrective is to counter the conflation of Delgado's and Freeman's life and work. Appreciating their distinctive legacies can help guide neuropsychiatric research done today that might yet haunt future generations.

Dysfunction in the prefrontal cortex is commonly implicated in anxiety disorders, but the mechanisms remain unclear. Approach-avoidance conflict tasks have been extensively used in animal research to better understand how changes in neural activity within the prefrontal cortex contribute to avoidance behaviors, which are believed to play a major role in the maintenance of anxiety disorders. In this article, we first review studies utilizing in vivo electrophysiology to reveal the relationship between changes in neural activity and avoidance behavior in rodents. We then review recent studies that take advantage of optical and genetic techniques to test the unique contribution of specific prefrontal cortex circuits and cell types to the control of anxiety-related avoidance behaviors. This new body of work reveals that behavior during approach-avoidance conflict is dynamically modulated by individual cell types, distinct neural pathways, and specific oscillatory frequencies. The integration of these different pathways, particularly as mediated by interactions between excitatory and inhibitory neurons, represents an exciting opportunity for the future of understanding anxiety.

What is the role of the brain's ongoing activity for cognition? The predominant perspectives associate ongoing brain activity with resting state, the default-mode network (DMN), and internally oriented mentation. This triad is often contrasted with task states, non-DMN brain networks, and externally oriented mentation, together comprising a "dual model" of brain and cognition. In opposition to this duality, however, we propose that ongoing brain activity serves as a neuronal baseline; this builds upon Raichle's original search for the default mode of brain function that extended beyond the canonical default-mode brain regions. That entails what we refer to as the "baseline model." Akin to an internal biological clock for the rest of the organism, the ongoing brain activity may serve as an internal point of reference or standard by providing a shared neural code for the brain's rest as well as task states, including their associated cognition. Such shared neural code is manifest in the spatiotemporal organization of the brain's ongoing activity, including its global signal topography and dynamics like intrinsic neural timescales. We conclude that recent empirical evidence supports a baseline model over the dual model; the ongoing activity provides a global shared neural code that allows integrating the brain's rest and task states, its DMN and non-DMN, and internally and externally oriented cognition.

Alzheimer's disease (AD) poses a critical public health challenge, and there is an urgent need for novel treatment options. Glutamate, the principal excitatory neurotransmitter in the human brain, plays a critical role in mediating cognitive and behavioral functions; and clinical symptoms in AD patients are highly correlated with the loss of glutamatergic synapses. In this review, we highlight how dysregulated glutamatergic mechanisms can underpin cognitive and behavioral impairments and contribute to the progression of AD via complex interactions with neuronal and neural network hyperactivity, Aβ, tau, glial dysfunction, and other disease-associated factors. We focus on the tripartite synapse, where glutamatergic neurotransmission occurs, and evidence elucidating how the tripartite synapse can be pathologically altered in AD. We also discuss promising therapeutic approaches that have the potential to rescue these deficits. These emerging data support the development of novel glutamatergic drug candidates as compelling approaches for treating AD.