bioRxiv Subject Collection: Neuroscience's Journal
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Monday, December 18th, 2023
| Time |
Event |
| 12:47a |
Estradiol regulates local synthesis of synaptic proteome via sex-specific mechanisms.
Estrogens, specifically 17{beta}-estradiol (estradiol), can modulate synaptic function by regulating the expression and localisation of synaptic proteins. However, the mechanisms underlying estradiols regulation of synaptic protein expression, and whether if they occur in a sex specific manner, is not well understood. In this study, using sex-specific hippocampal slice cultures and mixed-sex primary hippocampal neurons, we investigated whether local protein synthesis is required for estradiol-induced synaptic protein expression. Estradiol rapidly increased the rate of protein synthesis and the number of actively translating ribosomes along dendrites and near synapses in both male and female hippocampal neurons. Importantly, these effects occurred independently of gene transcription. Moreover, estradiol also increased the abundance of nascent proteins localised to synapses, independently of gene transcription. Specifically, estradiol increased the synaptic expression of GluN2B-containing N-methyl-D-aspartate receptors and PSD-95 in male and female hippocampus. Mechanistically, mTOR signalling was required for estradiol-induced increases in overall local protein synthesis only in male but not female hippocampus. Consistent with this, mTOR signalling mediated estradiol increases in GluN2B in male, but not female, hippocampus. Conversely, mTOR inhibition, blocked estradiol-induced increased PSD-95 expression in both male and female hippocampus. Collectively, these data suggest that the rapid modulation of local protein synthesis by estradiol is required for changes in the synaptic proteome in male and female hippocampus, and that the requirement of the mTOR signalling pathway in these effects occur in both a sex-specific and protein-dependent manner, with this signalling pathway have a greater role in male compared to female hippocampus. | | 12:47a |
Age-Related Changes of Dopamine D1 and D2 Receptors Expression in Parvalbumin-Positive Cells of the Orbitofrontal and Prelimbic Cortices of Mice
Dopamine (DA) plays a pivotal role in reward processing, cognitive functions, and emotional regulation. The prefrontal cortex (PFC) is a critical brain region for these processes. Parvalbumin-positive (PV+) neurons are one of the major classes of inhibitory GABAergic neurons in the cortex, they modulate the activity of neighboring neurons, influencing various brain functions. While DA receptor expression exhibits age-related changes, the age-related changes of these receptors in PV+ neurons, especially in the PFC, remains unclear. To address this, we investigated the expression of DA D1 (D1R) and D2 (D2R) receptors in PV+ neurons within the orbitofrontal (OFC) and prelimbic (PrL) cortices at different postnatal ages (P28, P42, P56, and P365). We found that the expression of D1R and D2R in PV+ neurons showed both age- and region-related changes. PV+ neurons in the OFC expressed a higher abundance of D1 than those in the PrL, and those neurons in the OFC also showed higher co-expression of D1R and D2R than those in the PrL. In both the OFC and PrL, D1R in PV+ neurons increased from P28 and reached a plateau at P42, then receded to express at P365. Meanwhile, D2R did not show significant age-related changes in both regions. These results showed dopamine receptors in the prefrontal cortex exhibit age- and region-specific changes, which may contribute to the difference of these brain regions in reward-related brain functions. | | 12:47a |
Molecular Disambiguation of Heart Rate Control by the Nucleus Ambiguus
The nucleus ambiguus (nAmb) provides parasympathetic control of cardiorespiratory functions as well as motor control of the upper airways and striated esophagus. A subset of nAmb neurons innervates the heart through the vagus nerve to control cardiac function at rest and during key autonomic reflexes such as the mammalian diving reflex. These cardiovagal nAmb neurons may be molecularly and anatomically distinct, but how they differ from other nAmb neurons in the adult brain remains unclear. We therefore classified adult mouse nAmb neurons based on their genome-wide expression profiles, innervation of cardiac ganglia, and ability to control HR. Our integrated analysis of single-nucleus RNA-sequencing data predicted multiple molecular subtypes of nAmb neurons. Mapping the axon projections of one nAmb neuron subtype, Npy2r-expressing nAmb neurons, showed that they innervate cardiac ganglia. Optogenetically stimulating all nAmb vagal efferent neurons dramatically slowed HR to a similar extent as selectively stimulating Npy2r+ nAmb neurons, but not other subtypes of nAmb neurons. Finally, we trained mice to perform voluntary underwater diving, which we use to show Npy2r+ nAmb neurons are activated by the diving response, consistent with a cardiovagal function for this nAmb subtype. These results together reveal the molecular organization of nAmb neurons and its control of heart rate. | | 1:19a |
"Cortical Delta" In The Medulla Of Sleeping Infant Rats
In early development when sleep is the most prevalent behavioral state, active (REM) sleep is preeminent before it is supplanted by quiet (non-REM) sleep. In rats, the developmental increase in quiet sleep is accompanied by the sudden emergence of the cortical delta rhythm (0.5-4 Hz) around postnatal day (P) 12. We sought to explain the emergence of cortical delta by assessing developmental changes in the activity of the parafacial zone (PZ), a medullary structure thought to regulate quiet sleep in adults. We recorded from PZ and predicted an age-related increase in neural activity during increasing periods of delta-rich cortical activity. Instead, we discovered a state-dependent pattern of neural activity comprising rhythmic bursts (separated by periods of complete silence) that are phase-locked to a local delta rhythm. Moreover, PZ and cortical delta were coherent at P12, but not at P10. PZ delta was also phase-locked to respiration, suggesting that reported links between respiration and cortical delta are traceable to sleep-dependent modulation of PZ activity by respiratory pacemakers in the ventral medulla. Disconnecting the main olfactory bulbs from the cortex did not diminish cortical delta, indicating that the influence of respiration on delta at this age is not mediated indirectly through nasal breathing. Finally, we observed increasing expression of parvalbumin-expressing terminals in PZ across these ages, supporting a role for GABAergic inhibition in PZ's rhythmicity. The discovery of delta-rhythmic neural activity in the medulla, at the moment of cortical delta's developmental emergence, opens a new path to understanding the brainstem's role in regulating quiet sleep. | | 3:18a |
Action history and target uncertainty co-determine human reaching direction under time pressure
Given the inaccuracies that are inherent in biological sensory and motor functions, animal sensorimotor control should be probabilistic. Effective neural control systems for movement must estimate the most likely true state of the world on the basis of uncertain sensory information, and to select and execute movements that are most likely to be successful given motor variability. Bayesian inference dictates that, if sensory information is ambiguous (e.g. low light conditions), animals should rely more on their past experience of target locations to guide motor planning, and less on their current sensory information about target location. Here we investigated how time pressure affects degree to which the precision of sensory information about a target influences movement direction bias towards previous target locations. We used a paradigm developed by Dekleva et al. (2016) that involved uncertain cues to the location of a hidden target for reaching with movement preparation time strictly controlled. One group of participants (n=10) were required to initiate their reaches within 150-300ms of target presentation, and a second group were required to initiate their reaches with 1150-1300ms of target presentation. We found that participants relied more on prior target location information when target precision was reduced under time pressure, which suggests that integration of target uncertainty information according to Bayesian principles is an inherent component of sensorimotor transformation and does not require time-consuming cognitive processes. | | 7:49p |
Contextual modulation of primary visual cortex by temporal predictability during motion extrapolation
Predicting future events is a fundamental cognitive ability which often depends on the volatility of the environment. Previous studies on apparent motion reported that when the brain is confronted with low levels of predictability, activity in low-level sensory areas is increased, including primary visual cortex. However, other studies on temporal predictability reported opposite effects potentially due to the influence of attention. It remains unclear, however, how temporal predictability modulates brain responses in a more ecologically valid real motion paradigm. Our study investigated whether motion extrapolation in high and low predictable contexts would differently modulate fMRI-responses in subject-specific primary visual cortex during visible and partially occluded stimulation. To this end, participants performed a modified version of the interception paradigm in visible and occluded phases, in which they observed a stimulus moving horizontally, then vertically at two different velocities. They were instructed to press when and where the stimulus would reach a given point-of-contact. In high predictable context, the velocity was identical during horizontal and vertical (occluded) movement; whereas, in low predictable context, the velocity could change during the vertical trajectory. MVPA results revealed accuracies above chance for all classification analyses carried out with low and highly predictable context data. Moreover, trial-history analysis showed that a change in trial type (constant velocity after change in velocity and vice versa) increased BOLD-responses in V1. This pattern of results suggests motion extrapolation can enhance activity in primary visual cortex, regardless of trial-specific predictability, but it is affected by recent trial history. |
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