bioRxiv Subject Collection: Neuroscience's Journal
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Monday, April 8th, 2024
| Time |
Event |
| 7:52a |
Morphometrical asymmetries and tractography of speech-relevant cortex in relation to language lateralisation and rapid temporal processing
Differences in the functional roles of the left and right cortices for speech-related processes have been known since the findings of Broca and Wernicke. Nearly 100 years later anatomical asymmetries of speech-related cortex was emphasised as a potential substrate to such functional lateralisations. Exploration of associations of anatomical asymmetries and functional lateralisations in speech has since continued, with developing technologies and theoretical insights mutually affording increasingly refined understandings. The present study is another such continuance; we outline and report associations of neuroanatomical (morphometrical) and connective (diffusion tractography) measures of speech-related cortex with differences of participant speech lateralisation and rapid temporal acuity (a hypothesised general auditory ability that contributes to superior speech processing). Review and support of developments in methodological approaches to morphometry and tractography to are also provided. Overall, our study affirms complex and selectively overlapping relationships of anatomy and connectivity (especially in the planum temporale) with behavioural language lateralisation and the processing of rapid temporal acoustics. Implications, limitations, and recommendations are discussed. | | 10:31a |
Activation of hypoactive parvalbumin-positive fast-spiking interneuron restores dentate inhibition to prevent epileptiform activity in the mouse intrahippocampal kainate model of temporal lobe epilepsy
Parvalbumin-positive (PV+) GABAergic interneurons in the dentate gyrus provide powerful perisomatic inhibition of dentate granule cells (DGCs) to prevent overexcitation and maintain the stability of dentate gyrus circuits. Most dentate PV+ interneurons survive status epilepticus, but surviving PV+ interneuron mediated inhibition is compromised in the dentate gyrus shortly after status epilepticus, contributing to epileptogenesis in temporal lobe epilepsy. It is uncertain whether the impaired activity of dentate PV+ interneurons recovers at later times or if it continues for months following status epilepticus. The development of compensatory modifications related to PV+ interneuron circuits in the months following status epilepticus is unknown, although reduced dentate GABAergic inhibition persists long after status epilepticus. We employed PV immunostaining and whole-cell patch-clamp recordings from dentate PV+ interneurons and DGCs in slices from male and female sham controls and intrahippocampal kainate (IHK) treated mice that developed spontaneous seizures months after status epilepticus to study epilepsy-associated changes in dentate PV+ interneuron circuits. We found that the number of dentate PV+ cells was reduced in IHK treated mice. Electrical recordings showed that: 1) Action potential firing rates of dentate PV+ interneurons were reduced in IHK treated mice up to four months after status epilepticus; 2) Spontaneous inhibitory postsynaptic currents (sIPSCs) in DGCs exhibited reduced frequency but increased amplitude in IHK treated mice; and 3) The amplitude of evoked IPSCs in DGCs by optogenetic activation of dentate PV+ cells was upregulated without changes in short-term plasticity. Video-EEG recordings revealed that IHK treated mice showed spontaneous epileptiform activity in the dentate gyrus and that chemogenetic activation of PV+ interneurons abolished the epileptiform activity. Our results suggest not only that the compensatory changes in PV+ interneuron circuits develop after IHK treatment, but also that increased PV+ interneuron mediated inhibition in the dentate gyrus may compensate for cell loss and reduced intrinsic excitability of dentate PV+ interneurons to stop seizures in temporal lobe epilepsy.
HighlightsO_LIReduced number of dentate PV+ interneurons in TLE mice
C_LIO_LIPersistently reduced action potential firing rates of dentate PV+ interneurons in TLE mice
C_LIO_LIEnhanced amplitude but decreased frequency of spontaneous IPSCs in the dentate gyrus in TLE mice
C_LIO_LIIncreased amplitude of evoked IPSCs mediated by dentate PV+ interneurons in TLE mice
C_LIO_LIChemogenetic activation of PV+ interneurons prevents epileptiform activity in TLE mice
C_LI | | 10:31a |
Accumbens Nitrergic Interneurons Drive the Cell Type-Specific Synaptic Plasticity Required for Cue-Induced Cocaine Seeking
Cocaine use disorder (CUD) remains a serious public health crisis, with relapse vulnerability continuing to pose the largest impediment to effective clinical treatment. Relapse to cocaine seeking is often triggered by drug craving evoked by exposure to drug-associated environmental cues. Data from preclinical models of rodent self-administration (SA) and cue-induced reinstatement demonstrate that exposure to drug predictive cues following a period of withdrawal engages a large induction of glutamate release in the nucleus accumbens core (NAc), not observed during cued sucrose seeking. This profound glutamate release engages neuronal nitric oxide synthase (nNOS) expressing interneurons likely through activation of metabotropic glutamate receptor 5 (mGluR5), leading to increased production of nitric oxide (NO). Importantly, cue-induced glutamate and NO production have been linked to activation of matrix metalloproteinases (MMPs) and induction of the transient synaptic plasticity in medium spiny neurons (MSNs) required for cued cocaine seeking. Recent evidence suggests that cue-induced structural and synaptic plasticity occurs predominantly in D1 Dopamine receptor expressing MSNs, yet despite these findings, how cue-induced glutamate release is translated into D1 MSN plasticity has yet to be elucidated. We show here that knockdown of nNOS is sufficient to block cue-induced reinstatement to cocaine and prevents cue-induced functional and structural synaptic adaptions specifically in D1 receptor containing MSNs. Next, we demonstrate that knockdown of mGluR5, selectively on nitrergic interneurons in the NAc, is sufficient to block both conditioned place preference (CPP) and cue-induced reinstatement to cocaine, mechanistically linking cue-associated glutamate release to NO signaling. Finally, we demonstrate that downstream of glutamate-mediated activation of mGluR5 on nitrergic interneurons and MMP activation, expression of B3 integrin receptors on D1 MSNs is required for cued cocaine seeking. Taken together, our data provide a mechanistic link between cocaine cue-induced glutamate release, activation of nitrergic interneurons and the D1 MSN plasticity required for cued cocaine seeking, | | 8:47p |
Interneuron diversity and normalization specificity in a visual system
Normalization is a fundamental operation in image processing. Convolutional nets have evolved over the past decade to include a large number of normalizations, and this architectural shift has proved essential for robust visual artificial intelligence. Here I argue that normalization is the function of a large fraction of neuronal cell types in the fly optic lobe. A dozen types of local interneuron in the distal medulla (Dm), in particular, are argued to mediate lateral inhibition, which was classically assumed to depend only on spatial separation. Each Dm type turns out to connect with specific source and target cell types. The source and target are either the same type, or are directly connected, from which it follows that Dm-mediated lateral inhibition has a normalizing function. Therefore the diversity of Dm interneurons is analogous to the ubiquity of normalizations in contemporary convolutional nets. A notable difference is that Dm types normalize over specific spatial scales. A final Dm type is an outlier in its perfect tiling of the medulla, and likely does not mediate lateral inhibition due to a predicted electrical compartmentalization of its arbor. Further candidate normalizers are identified in all other interneuron families, generalizing the Dm findings to the entire optic lobe. | | 8:47p |
The fluctuation-dissipation theorem and the discovery of distinctive off-equilibrium signatures of brain states
The brain is able to sustain many different states as shown by the daily natural transitions between wakefulness and sleep. Yet, the underlying complex dynamics of these brain states are essentially in non-equilibrium. Here, we develop a thermodynamical formalism based on the off-equilibrium extension of the fluctuation-dissipation theorem (FDT) together with a whole-brain model. This allows us to investigate the non-equilibrium dynamics of different brain states and more specifically to apply this formalism to wakefulness and deep sleep brain states. We show that the off-equilibrium thermodynamical signatures of brain states are significantly different in terms of the overall level of differential and integral violation of FDT. Furthermore, the framework allows for a detailed understanding of how different brain regions and networks are contributing to the off-equilibrium signatures in different brain states. Overall, this framework shows great promise for characterising and differentiating any brain state in health and disease. |
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