Biology subjects

Lundqvist, M.

Publications and source records attributed to Lundqvist, M..

30 records · Page 2Linked to original sources

bioRxiv2021

Traveling waves in the prefrontal cortex during working memory

Neural oscillations are evident across cortex but their spatial structure is not well-explored. Are oscillations stationary or do they form "traveling waves", i.e., spatially organized patterns whose peaks and troughs move sequentially across cortex? Here, we show that oscillations in the prefrontal cortex (PFC) organized as traveling waves in the theta (4-8Hz), alpha (8-12Hz) and beta (12-30Hz) bands. Some traveling waves were planar but most rotated. The waves were modulated during performance of a working memory task. During baseline conditions, waves flowed bidirectionally along a specific axis of orientation. Waves in different frequency bands could travel in different directions. During task performance, there was an increase in waves in one direction over the other, especially in the beta band. Author SummaryWe found that oscillations in the prefrontal cortex form "traveling waves". Traveling waves are spatially extended patterns in which aligned peaks of activity move sequentially across the cortical surface. Some traveling waves were planar but most rotated. The prefrontal cortex is important for working memory. The traveling waves changed when monkeys performed a working memory task. There was an increase in waves in one direction over the other, especially in the beta band. Traveling waves can serve specific functions. For example, they help maintain network status and help control timing relationships between spikes. Given their functional advantages, a greater understanding of traveling waves should lead to a greater understanding of cortical function.

neuroscience↗

bioRxiv2021

ODOR IDENTITY CAN BE EXTRACTED FROM THE RECIPROCAL CONNECTIVITY BETWEEN OLFACTORY BULB AND PIRIFORM CORTEX IN HUMANS

Neuronal oscillations route external and internal information across brain regions. In the olfactory system, the two central nodes--the olfactory bulb (OB) and the piriform cortex (PC)--communicate with each other via neural oscillations to shape the olfactory percept. Communication between these nodes have been well characterized in non-human animals but less is known about their role in the human olfactory system. Using a recently developed and validated EEG-based method to extract signals from the OB and PC sources, we show in healthy human participants that there is a bottom-up information flow from the OB to the PC in the beta and gamma frequency bands, while top-down information from the PC to the OB is facilitated by delta and theta oscillations. Importantly, we demonstrate that there was enough information to decipher odor identity above chance from the low gamma in the OB-PC oscillatory circuit as early as 100ms after odor onset. These data further our understanding of the critical role of bidirectional information flow in human sensory systems to produce perception. However, future studies are needed to determine what specific odor information is extracted and communicated in the information exchange.

neuroscience↗

bioRxiv2021

A Hot-Coal theory of Working Memory

Working memory (WM) allows us to selectively remember and flexibly control a limited amount of information. Earlier work has suggested WM control is achieved by interactions between bursts of beta and gamma oscillations. The emerging question is how beta and gamma bursting, reflecting coherent activity of hundreds of thousands of neurons, can underlie selective control of individual items held in WM? Here, we propose a principle for how such selective control might be achieved on the neural network level. It relies on spatial computing, which suggests that beta and gamma interactions cause item-specific activity to flow spatially across the network over the course of a task. This way, control-related information about, for instance, item order can be retrieved from the spatial activity independent of the detailed recurrent connectivity that gives rise to the item-specific activity itself. The spatial flow should in turn be reflected in low-dimensional activity shared by many neurons. We test predictions of the proposed spatial computing paradigm by analysing control-related as well as item-specific activity in local field potentials and neuronal spiking from prefrontal cortex of rhesus macaques performing four WM tasks. As predicted, we find that the low-dimensional activity has a spatial component from which we can read out control-related information. These spatial components were stable over multiple sessions and did not depend on the specific WM items being used. We hypothesize that spatial computing can facilitate generalization and zero-shot learning by utilizing spatial component as an additional information encoding dimension. This offers a new perspective on the functional role of low-dimensional activity that tends to dominate cortical activity.

neuroscience↗

bioRxiv2020

Interhemispheric transfer of working memories

Visual working memory (WM) storage is largely independent between the left and right visual hemifields/cerebral hemispheres, yet somehow WM feels seamless. We studied how WM is integrated across hemifields by recording neural activity bilaterally from lateral prefrontal cortex. An instructed saccade during the WM delay shifted the remembered location from one hemifield to the other. Before the shift, spike rates and oscillatory power showed clear signatures of memory laterality. After the shift, the lateralization inverted, consistent with transfer of the memory trace from one hemisphere to the other. Transferred traces initially used different neural ensembles from feedforward-induced ones but they converged at the end of the delay. Around the time of transfer, synchrony between the two prefrontal hemispheres peaked in theta and beta frequencies, with a directionality consistent with memory trace transfer. This illustrates how dynamics between the two cortical hemispheres can stitch together WM traces across visual hemifields.

neuroscience↗

bioRxiv2020

Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation

The specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency (~1 Hz) oscillations in local field potentials, entrainment of local spiking to Up states alternating with Down states of little spiking, and decreased coherence in frequencies above 4 Hz. Thalamic stimulation "awakened" anesthetized NHPs and reversed the electrophysiologic features of unconsciousness. Unconsciousness is linked to cortical and thalamic slow frequency synchrony coupled with decreased spiking, and loss of higher-frequency dynamics. This may disrupt cortical communication/integration.

neuroscience↗

bioRxiv2020

Amyloid-β oligomers are captured by the DNAJB6 chaperone: Direct detection of interactions that can prevent primary nucleation

A human molecular chaperone protein, DNAJB6, is an efficient inhibitor of amyloid aggregation owing to a unique motif with conserved S/T-residues with high capacity for hydrogen bonding. Global analysis of kinetics data previously showed that especially the primary nucleation rate is inhibited. It was concluded that DNAJB6 achieves this remarkably effective and sub-stoichiometric inhibition by interacting not with the monomeric unfolded conformations of the amyloid-{beta} (A{beta}) peptide but with aggregated species. The pre-nucleation oligomeric aggregates are transient and difficult to study experimentally. Here we employed an approach to directly detect oligomeric forms of A{beta} formed in solution by subsequent analysis with native mass spectrometry (native MS). Results show that the signals from the various forms of A{beta} (1-40) oligomers were reduced considerably in the presence of DNAJB6, but not with a mutational variant of DNAJB6 in which the S/T-residues were substituted. With focus on DNAJB6 we could also detect signals that appear to represent DNAJB6 dimers and trimers to which varying amounts of A{beta} is bound. These data provide direct experimental evidence that it is the oligomeric forms of A{beta} that are captured by DNAJB6 in a manner which is dependent on the S/T residues. Strong binding of A{beta} oligomers to DNAJB6 should indeed inhibit the formation of amyloid nuclei, in agreement with the previously observed decrease in primary nucleation rate.

biochemistry↗

bioRxiv2020

Evolution from adherent to suspension - systems biology of HEK293 cell line development

The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production and is today used for manufacturing of several therapeutic proteins and viral vectors. Despite this increasing popularity there is still limited knowledge of the detailed genetic and composition of derivatives of this strain. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.

systems biology↗

bioRxiv2020

Layer and rhythm specificity for predictive routing

In predictive coding, experience generates predictions that attenuate the feeding forward of predicted stimuli while passing forward unpredicted "errors". Different models have different neural implementations of predictive coding. We recorded spikes and local field potentials from laminar electrodes in five cortical areas (V4, LIP, area 7A, FEF, and PFC) while monkeys performed a task that modulated visual stimulus predictability. Pre-stimulus predictions were associated with increased alpha/beta (8-30 Hz) power/coherence that fed back the cortical hierarchy primarily via deep-layer cortex. Unpredictable stimuli were associated with increases in spiking and in gamma-band (40-90 Hz) power/coherence that fed forward up the cortical hierarchy via superficial-layer cortex. Area 7A uniquely showed increases in high-beta (~22-28 Hz) power/coherence to unpredicted stimuli. These results suggest that predictive coding may be implemented via lower-frequency alpha/beta rhythms that "prepare" pathways processing predicted inputs by inhibiting feedforward gamma rhythms and associated spiking.

neuroscience↗

bioRxiv2020

Achieving stable dynamics in neural circuits

1The brain consists of many interconnected networks with time-varying, partially autonomous activity. There are multiple sources of noise and variation yet activity has to eventually converge to a stable, reproducible state (or sequence of states) for its computations to make sense. We approached this problem from a control-theory perspective by applying contraction analysis to recurrent neural networks. This allowed us to find mechanisms for achieving stability in multiple connected networks with biologically realistic dynamics, including synaptic plasticity and time-varying inputs. These mechanisms included inhibitory Hebbian plasticity, excitatory anti-Hebbian plasticity, synaptic sparsity and excitatory-inhibitory balance. Our findings shed light on how stable computations might be achieved despite biological complexity.

neuroscience↗

bioRxiv2019

How neural circuits achieve and use stable dynamics

1The brain consists of many interconnected networks with time-varying activity. There are multiple sources of noise and variation yet activity has to eventually converge to a stable state for its computations to make sense. We approached this from a control-theory perspective by applying contraction analysis to recurrent neural networks. This allowed us to find mechanisms for achieving stability in multiple connected networks with biologically realistic dynamics, including synaptic plasticity and time-varying inputs. These mechanisms included anti-Hebbian plasticity, synaptic sparsity and excitatory-inhibitory balance. We leveraged these findings to construct networks that could perform functionally relevant computations in the presence of noise and disturbance. Our work provides a blueprint for how to construct stable plastic and distributed networks.

neuroscience↗

bioRxiv2018

The human secretome - the proteins secreted from human cells

The proteins secreted by human tissues (the secretome) are important for the basic understanding of human biology, but also for identification of potential targets for future diagnosis and therapy. Here, we present an annotation of all predicted secreted proteins (n=2,623) with information about their spatial distribution in the human body. A high-throughput mammalian cell factory was established to create a resource of recombinant full-length proteins. This resource was used for phenotypic assays involving {beta}-cell dedifferentiation and for development of targeted proteomics assays. A comparison between host cells, including omics analysis, shows that many of the proteins that failed to be generated in CHO cells could be rescued in human HEK293 cells. In conclusion, the human secretome has been mapped and characterized to facilitate further exploration of the human secretome.

molecular biology↗

bioRxiv2017

Gamma and beta bursts during working memory read-out suggest roles in its volitional control

Working memory (WM) activity is not as stationary or sustained as previously thought. There are brief bursts of gamma ([~]55-120 Hz) and beta ([~]20-35 Hz) oscillations, the former linked to stimulus information in spiking. We examine these dynamics in relation to read-out from WM, which is still not well understood. Monkeys held a sequence of two objects and had to decide if they matched a subsequent sequence. Changes in the balance of beta/gamma suggested their role in WM control. In anticipation of having to use an object for the match decision, there was an increase in spiking information about that object along with an increase in gamma and a decrease in beta. When an object was no longer needed, beta increased and gamma as well as spiking information about that object decreased. Deviations from these dynamics predicted behavioral errors. Thus, turning up or down beta could regulate gamma and the information in working memory.

neuroscience↗