{"title":"Neuronal threshold functions: Determining symptom onset in neurological disorders","authors":"Luc Jordi , Ole Isacson","doi":"10.1016/j.pneurobio.2024.102673","DOIUrl":"10.1016/j.pneurobio.2024.102673","url":null,"abstract":"<div><div>Synaptic networks determine brain function. Highly complex interconnected brain synaptic networks provide output even under fluctuating or pathological conditions. Relevant to the treatment of brain disorders, understanding the limitations of such functional networks becomes paramount. Here we use the example of Parkinson’s Disease (PD) as a system disorder, with PD symptomatology emerging only when the functional reserves of neurons, and their interconnected networks, are unable to facilitate effective compensatory mechanisms. We have denoted this the “threshold theory” to account for how PD symptoms develop in sequence. In this perspective, threshold functions are delineated in a quantitative, synaptic, and cellular network context. This provides a framework to discuss the development of specific symptoms. PD includes dysfunction and degeneration in many organ systems and both peripheral and central nervous system involvement. The threshold theory accounts for and explains the reasons why parallel gradually emerging pathologies in brain and peripheral systems generate specific symptoms only when functional thresholds are crossed, like tipping points. New and mounting evidence demonstrate that PD and related neurodegenerative diseases are multisystem disorders, which transcends the traditional brain-centric paradigm. We believe that representation of threshold functions will be helpful to develop new medicines and interventions that are specific for both pre- and post-symptomatic periods of neurodegenerative disorders.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"242 ","pages":"Article 102673"},"PeriodicalIF":6.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael A. Hahn , Janna D. Lendner , Matthias Anwander , Katarina S.J. Slama , Robert T. Knight , Jack J. Lin , Randolph F. Helfrich
{"title":"A tradeoff between efficiency and robustness in the hippocampal-neocortical memory network during human and rodent sleep","authors":"Michael A. Hahn , Janna D. Lendner , Matthias Anwander , Katarina S.J. Slama , Robert T. Knight , Jack J. Lin , Randolph F. Helfrich","doi":"10.1016/j.pneurobio.2024.102672","DOIUrl":"10.1016/j.pneurobio.2024.102672","url":null,"abstract":"<div><div>Sleep constitutes a brain state of disengagement from the external world that supports memory consolidation and restores cognitive resources. The precise mechanisms how sleep and its varied stages support information processing remain largely unknown. Synaptic scaling models imply that daytime learning accumulates neural information, which is then consolidated and downregulated during sleep. Currently, there is a lack of in-vivo data from humans and rodents that elucidate if, and how, sleep renormalizes information processing capacities. From an information-theoretical perspective, a consolidation process should entail a reduction in neural pattern variability over the course of a night. Here, in a cross-species intracranial study, we identify a tradeoff in the neural population code during sleep where information coding efficiency is higher in the neocortex than in hippocampal archicortex in humans than in rodents as well as during wakefulness compared to sleep. Critically, non-REM sleep selectively reduces information coding efficiency through pattern repetition in the neocortex in both species, indicating a transition to a more robust information coding regime. Conversely, the coding regime in the hippocampus remained consistent from wakefulness to non-REM sleep. These findings suggest that new information could be imprinted to the long-term mnemonic storage in the neocortex through pattern repetition during sleep. Lastly, our results show that task engagement increased coding efficiency, while medically-induced unconsciousness disrupted the population code. In sum, these findings suggest that neural pattern variability could constitute a fundamental principle underlying cognitive engagement and memory formation, while pattern repetition reflects robust coding, possibly underlying the consolidation process.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"242 ","pages":"Article 102672"},"PeriodicalIF":6.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mario O. Caracci , Héctor Pizarro , Carlos Alarcón-Godoy , Luz M. Fuentealba , Pamela Farfán , Raffaella De Pace , Natacha Santibañez , Viviana A. Cavieres , Tammy P. Pástor , Juan S. Bonifacino , Gonzalo A. Mardones , María-Paz Marzolo
{"title":"Corrigendum to “The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for hereditary spastic paraplegia” [Progr. Neurobiol. 234(2024)102575]","authors":"Mario O. Caracci , Héctor Pizarro , Carlos Alarcón-Godoy , Luz M. Fuentealba , Pamela Farfán , Raffaella De Pace , Natacha Santibañez , Viviana A. Cavieres , Tammy P. Pástor , Juan S. Bonifacino , Gonzalo A. Mardones , María-Paz Marzolo","doi":"10.1016/j.pneurobio.2024.102662","DOIUrl":"10.1016/j.pneurobio.2024.102662","url":null,"abstract":"","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"241 ","pages":"Article 102662"},"PeriodicalIF":6.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Azadeh Feizpour , Mark J. Buckley , Inaki C. Mundinano , Marcello G.P. Rosa , Farshad Alizadeh Mansouri
{"title":"The role of frontopolar cortex in adjusting the balance between response execution and action inhibition in anthropoids","authors":"Azadeh Feizpour , Mark J. Buckley , Inaki C. Mundinano , Marcello G.P. Rosa , Farshad Alizadeh Mansouri","doi":"10.1016/j.pneurobio.2024.102671","DOIUrl":"10.1016/j.pneurobio.2024.102671","url":null,"abstract":"<div><div>Executive control of behaviour entails keeping a fine balance between response execution and action inhibition. The most anterior part of the prefrontal cortex (frontopolar cortex) is highly developed in anthropoids; however, no previous study has examined its essential (indispensable) role in regulating the interplay between action execution and inhibition. In this cross-species study, we examine the performance of humans and macaque monkeys in the context of a stop-signal task and then assess the consequence of selective and bilateral damage to frontopolar cortex on monkeys’ behaviour. Humans and monkeys showed significant within-session practice-related adjustments in both response execution (increase in response time (RT) and decrease in response variabilities) and action inhibition (enhanced inhibition). Furthermore, both species expressed context-dependent (post-error and post-stop) behavioral adjustments. In post-lesion testing, frontopolar-damaged monkeys had a longer RT and lower percentage of timeout trials, compared to their pre-lesion performance. The practice-related changes in mean RT and in RT variability were significantly heightened in frontopolar-damaged monkeys. They also showed attenuated post-error, but exaggerated post-stop, behavioural adjustments. Importantly, frontopolar damage had no significant effects on monkeys’ inhibition ability. Our findings indicate that frontopolar cortex plays a critical role in allocation of control to response execution, but not action inhibition.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"241 ","pages":"Article 102671"},"PeriodicalIF":6.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sparse representation of neurons for encoding complex sounds in the auditory cortex","authors":"HiJee Kang , Patrick O. Kanold","doi":"10.1016/j.pneurobio.2024.102661","DOIUrl":"10.1016/j.pneurobio.2024.102661","url":null,"abstract":"<div><div>Listening in complex sound environments requires rapid segregation of different sound sources, e.g., having a conversation with multiple speakers or other environmental sounds. Efficient processing requires fast encoding of inputs to adapt to target sounds and identify relevant information from past experiences. This adaptation process represents an early phase of implicit learning of the sound statistics to form auditory memory. The auditory cortex (ACtx) plays a crucial role in this implicit learning process, but the underlying circuits are unknown. In awake mice, we recorded neuronal responses in different ACtx subfields using in vivo 2-photon imaging of excitatory and inhibitory (parvalbumin; PV) neurons. We used a paradigm adapted from human studies that induced rapid implicit learning from passively presented complex sounds and imaged A1 Layer 4 (L4), A1 L2/3, and A2 L2/3. In this paradigm, a frozen spectro-temporally complex <em>‘Target’</em> sound randomly re-occurred within a stream of other random complex sounds. All ACtx subregions contained distinct groups of cells specifically responsive to complex acoustic sequences, indicating that even thalamocortical input layers (A1 L4) respond to complex sounds. Subgroups of excitatory and inhibitory cells in all subfields showed decreased responses for re-occurring Target sounds, indicating that ACtx is highly involved in the early implicit learning phase. At the population level, activity was more decorrelated to Target sounds independent of the duration of frozen token, subregions, and cell type. These findings suggest that ACtx and its input layers contribute to the early phase of auditory memory for complex sounds, suggesting a parallel strategy across ACtx areas and between excitatory and inhibitory neurons.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"241 ","pages":"Article 102661"},"PeriodicalIF":6.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elliot Murphy , Patrick S. Rollo , Katrien Segaert , Peter Hagoort , Nitin Tandon
{"title":"Multiple dimensions of syntactic structure are resolved earliest in posterior temporal cortex","authors":"Elliot Murphy , Patrick S. Rollo , Katrien Segaert , Peter Hagoort , Nitin Tandon","doi":"10.1016/j.pneurobio.2024.102669","DOIUrl":"10.1016/j.pneurobio.2024.102669","url":null,"abstract":"<div><div>How we combine minimal linguistic units into larger structures remains an unresolved topic in neuroscience. Language processing involves the abstract construction of ‘vertical’ and ‘horizontal’ information simultaneously (e.g., phrase structure, morphological agreement), but previous paradigms have been constrained in isolating only one type of composition and have utilized poor spatiotemporal resolution. Using intracranial recordings, we report multiple experiments designed to separate phrase structure from morphosyntactic agreement. Epilepsy patients (n = 10) were presented with auditory two-word phrases grouped into pseudoword-verb (‘trab run’) and pronoun-verb either with or without Person agreement (‘they run’ vs. ‘they runs’). Phrase composition and Person violations both resulted in significant increases in broadband high gamma activity approximately 300 ms after verb onset in posterior middle temporal gyrus (pMTG) and posterior superior temporal sulcus (pSTS), followed by inferior frontal cortex (IFC) at 500 ms. While sites sensitive to only morphosyntactic violations were distributed, those sensitive to both composition types were generally confined to pSTS/pMTG and IFC. These results indicate that posterior temporal cortex shows the earliest sensitivity for hierarchical linguistic structure across multiple dimensions, providing neural resources for distinct windows of composition. This region is comprised of sparsely interwoven heterogeneous constituents that afford cortical search spaces for dissociable syntactic relations.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"241 ","pages":"Article 102669"},"PeriodicalIF":6.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mnemonically modulated perceptual processing to represent allocentric space in macaque inferotemporal cortex","authors":"Ao Li , He Chen , Yuji Naya","doi":"10.1016/j.pneurobio.2024.102670","DOIUrl":"10.1016/j.pneurobio.2024.102670","url":null,"abstract":"<div><div>To encode allocentric space information of a viewing object, it is important to relate perceptual information in the first-person perspective to the representation of an entire scene which would be constructed before. A substantial number of studies investigated the constructed scene information (e.g., cognitive map). However, only few studies have focused on its influence on perceptual processing. Therefore, we designed a visually guided saccade task requiring monkeys to gaze at objects in different locations on different backgrounds clipped from large self-designed mosaic pictures (parental pictures). In each trial, we presented moving backgrounds prior to object presentations, indicating a frame position of the background image on a parental picture. We recorded single-unit activities from 377 neurons in the posterior inferotemporal (PIT) cortex of two macaques. Equivalent numbers of neurons showed space-related (119 of 377) and object-related (125 of 377) information. The space-related neurons coded the gaze locations and background images jointly rather than separately. These results suggest that PIT neurons represent a particular location within a particular background image. Interestingly, frame positions of background images on parental pictures modulated the space-related responses dependently on parental pictures. As the frame positions could be acquired by only preceding visual experiences, the present results may provide neuronal evidence of a mnemonic effect on current perception, which might represent allocentric object location in a scene beyond the current view.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"241 ","pages":"Article 102670"},"PeriodicalIF":6.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tanner L. Anderson , Jack V. Keady , Judy Songrady , Navid S. Tavakoli , Artin Asadipooya , Ryson E. Neeley , Jill R. Turner , Pavel I. Ortinski
{"title":"Distinct 5-HT receptor subtypes regulate claustrum excitability by serotonin and the psychedelic, DOI","authors":"Tanner L. Anderson , Jack V. Keady , Judy Songrady , Navid S. Tavakoli , Artin Asadipooya , Ryson E. Neeley , Jill R. Turner , Pavel I. Ortinski","doi":"10.1016/j.pneurobio.2024.102660","DOIUrl":"10.1016/j.pneurobio.2024.102660","url":null,"abstract":"<div><p>Recent evidence indicates that neuronal activity within the claustrum (CLA) may be central to cellular and behavioral responses to psychedelic hallucinogens. The CLA prominently innervates many cortical targets and displays exceptionally high levels of serotonin (5-HT) binding. However, the influence of serotonin receptors, prime targets of psychedelic drug action, on CLA activity remains unexplored. We characterize the CLA expression of all known 5-HT subtypes and contrast the effects of 5-HT and the psychedelic hallucinogen, 2,5-dimethoxy-4-iodoamphetamine (DOI), on excitability of cortical-projecting CLA neurons. We find that the CLA is particularly enriched with 5-HT2C receptors, expressed predominantly on glutamatergic neurons. Electrophysiological recordings from CLA neurons that project to the anterior cingulate cortex (ACC) indicate that application of 5-HT inhibits glutamate receptor-mediated excitatory postsynaptic currents (EPSCs). In contrast, application of DOI stimulates EPSCs. We find that the opposite effects of 5-HT and DOI on synaptic signaling can both be reversed by inhibition of the 5-HT2C, but not 5-HT2A, receptors. We identify specific 5-HT receptor subtypes as serotonergic regulators of the CLA excitability and argue against the canonical role of 5-HT2A in glutamatergic synapse response to psychedelics within the CLA-ACC circuit.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"240 ","pages":"Article 102660"},"PeriodicalIF":6.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}