Galanin, one of the most inducible neuropeptides, is widely present in developing brains, and its expression is altered by pathologic events (e.g., epilepsy, ischemia, and axotomy). The roles of galanin in brain development under both normal and pathologic conditions have been hypothesized, but the question of how galanin is involved in fetal and early postnatal brain development remains largely unanswered. In this study, using granule cell migration in the cerebellum of early postnatal mice (both sexes) as a model system, we examined the role of galanin in neuronal cell migration during normal development and after brain injury. Here we show that, during normal development, endogenous galanin participates in accelerating granule cell migration via altering the Ca2+ and cAMP signaling pathways. Upon brain injury induced by the application of cold insults, galanin levels decrease at the lesion sites, but increase in the surroundings of lesion sites. Granule cells exhibit the following corresponding changes ...

Racism is a threat to public health. Race is a sociopolitical construct that has been used for generations to create disparities in educational access, housing conditions, exposure to environmental contaminants, and access to health care. Collectively, these disparities have a negative impact on the health of non-white Americans. The National Institutes of Health (NIH) funds biomedical research, including basic neuroscience research, aimed at understanding the mechanisms and consequences of health and disease in Americans. NIH has recently acknowledged its own structural racism, the disadvantage this perpetuates in the biomedical research enterprise, and has announced its commitment to eliminating these disparities. Here, we discuss different rates of disease in U.S. citizens from different racial backgrounds. We next describe ways in which the biomedical research enterprise (1) has contributed to health disparities and (2) can contribute to the solving this problem. Based on our own scientific expertise, ...

Persistent anion conductances through GABAA receptors (GABAAR) are important modulators of neuronal excitability. However, it is currently unknown how the amplitudes of these currents vary amongst different cell types in the human neocortex, particularly amongst diverse GABAergic interneurons. We have recorded 101 interneurons in and near layer 1 from cortical tissue surgically resected from both male and female patients, visualised 84 of them and measured tonic GABAAR currents in 48 cells with an intracellular [Cl-] of 65 mM and in the presence of 5 µM GABA. We compare these tonic currents amongst five groups of interneurons divided by firing properties and four types of interneuron defined by axonal distributions; rosehip, neurogliaform, stalked-bouton, layers 2-3 innervating and a pool of other cells. Interestingly, the rosehip cell, a type of interneuron only described thus far in human tissue, and layers 2-3 innervating cells exhibit larger tonic currents than other layer 1 interneurons, such as neuro...

Persistent anion conductances through GABAA receptors (GABAAR) are important modulators of neuronal excitability. However, it is currently unknown how the amplitudes of these currents vary amongst different cell types in the human neocortex, particularly amongst diverse GABAergic interneurons. We have recorded 101 interneurons in and near layer 1 from cortical tissue surgically resected from both male and female patients, visualised 84 of them and measured tonic GABAAR currents in 48 cells with an intracellular [Cl-] of 65 mM and in the presence of 5 µM GABA. We compare these tonic currents amongst five groups of interneurons divided by firing properties and four types of interneuron defined by axonal distributions; rosehip, neurogliaform, stalked-bouton, layers 2-3 innervating and a pool of other cells. Interestingly, the rosehip cell, a type of interneuron only described thus far in human tissue, and layers 2-3 innervating cells exhibit larger tonic currents than other layer 1 interneurons, such as neuro...

Neural oscillations can couple networks of brain regions, especially at lower frequencies. The nasal respiratory rhythm, which elicits robust olfactory bulb oscillations, has been linked to episodic memory, locomotion, and exploration, along with widespread oscillatory coherence. The piriform cortex is implicated in propagating the olfactory-bulb-driven respiratory rhythm, but this has not been tested explicitly in the context of both hippocampal theta and nasal respiratory rhythm during exploratory behaviors. We investigated systemwide interactions during foraging behavior, which engages respiratory and theta rhythms. Local field potentials from the olfactory bulb, piriform cortex, dentate gyrus, and CA1 of hippocampus, primary visual cortex, and nasal respiration were recorded simultaneously from male rats. We compared interactions among these areas while rats foraged using either visual or olfactory spatial cues. We found high coherence during foraging compared with home cage activity in two frequency b...

We propose a model of the main rhythms in the hippocampal CA1 field: theta rhythm, slow, middle, and fast gamma rhythms, and ripples oscillations. We have based this on data obtained from animals behaving freely. We have considered the modes of neuronal discharges and the occurrence of local field potential (LFP) oscillations in the theta and non-theta states at different inputs from the CA3 field, the medial entorhinal cortex, and the medial septum. In our work, we tried to reproduce the main experimental phenomena about rhythms in the CA1 field: the coupling of neurons to the phase of rhythms, cross-rhythm phase-phase and phase-amplitude coupling. Using computational experiments, we have proved the hypothesis that the descending phase of the theta rhythm in the CA1 field is formed by the input from the CA3 field via the Shaffer collaterals, and the ascending phase of the theta rhythm is formed by the inhibitory postsynaptic potentials from CCK basket cells. The slow gamma rhythm is coupled to the descend...

Post-encoding coordinated reactivation of memory traces distributed throughout interconnected brain regions is thought to be critical for consolidation of memories. However, little is known about the role of neural circuit pathways during post-learning periods for consolidation of memories. To investigate this question, we optogenetically silenced the inputs from both auditory cortex (AuV/TeA) and thalamus (MGm/PIN) in the lateral amygdala (LA) for 15 min immediately following auditory fear conditioning (FC) and examined its effect on fear memory formation in mice of both sexes. Optogenetic inhibition of both inputs disrupted long-term fear memory formation tested 24 h after FC. This effect was specific such that the same inhibition did not affect short-term memory and context-dependent memory. Moreover, long-term memory was intact if the inputs were inhibited at much later time points after FC (3 h or 1 d after FC), indicating that optical inhibition for 15 min itself does not produce any non-specific del...

Memory reactivation during sleep reinforces various types of learning. Basic motor skills likely benefit from sleep. There is insufficient evidence, however, on whether memory reactivation during sleep contributes to learning how to execute a novel action. Here, we investigated motor learning in a myoelectric feedback task. Human male and female participants learned to control myoelectric activity in specific arm muscles to move a computer cursor to each of 16 locations. Each location was associated with a unique sound. Half of the sounds were played during slow-wave sleep to reactivate corresponding memories of muscle control. After sleep, movements cued during sleep were performed more quickly and efficiently than uncued movements. These results demonstrated that memory reactivation during sleep contributes to learning of action execution. We conclude that sleep supports learning novel actions, which also maps onto the learning required in certain neurorehabilitation procedures. SIGNIFICANCE STATEMENT: ...

Traumatic brain injury (TBI) results in disrupted brain function following impact from an external force and is a risk factor for sporadic Alzheimer’s Disease (AD). Though neurological symptoms triggered by mild traumatic brain injuries (mTBI) – the most common form of TBI – typically resolve rapidly, even an isolated mTBI event can increase the risk to develop AD. Aberrant accumulation of amyloid beta peptide (Aβ), a cleaved fragment of amyloid precursor protein (APP), is a key pathological outcome designating the progression of AD following mTBI and has also been linked to impaired axonal transport. However, relationships among mTBI, amyloidogenesis, and axonal transport remain unclear, in part due to the dearth of human models to study the neuronal response following mTBI. Here, we implemented a custom-microfabricated device to deform neurons derived from human induced pluripotent stem cells (hiPSC), derived from a cognitively unimpaired male individual, to mimic the mild stretch experienced by neurons ...

We tested how a stimulus gestalt, defined by the neuronal interaction between local and global features of a stimulus, is represented within human primary visual cortex (V1). We used high-resolution functional magnetic resonance imaging (fMRI), which serves as a surrogate of neuronal activation, to measure co-fluctuations within sub-regions of V1 as (male and female) subjects were presented with peripheral stimuli, each with different global configurations. We found stronger cross-hemisphere correlations when fine-scale V1 cortical sub-regions represented parts of the same object, as compared to different objects. This result was consistent with the vertical bias in global processing and, critically, was independent of the task and local discontinuities within objects. Thus, despite the relatively small receptive fields of neurons within V1, global stimulus configuration affects neuronal processing via correlated fluctuations between regions that represent different sectors of the visual field. SIGNIFICAN...