Ivan Soltesz

• Stanford University

The brain's endocannabinoid signaling system modulates a diverse range of physiological phenomena and is also involved in various psychiatric and neurological disorders. The basic components of the molecular machinery underlying endocannabinoid-mediated synaptic signaling have been known for decades. However, limitations associated with the short-l...

Visual place recognition (VPR) is the ability to recognize locations in a physical environment based only on visual inputs. It is a challenging task due to perceptual aliasing, viewpoint and appearance variations and complexity of dynamic scenes. Despite promising demonstrations, many state-of-the-art (SOTA) VPR approaches based on artificial neura...

The Hippocampus Book investigates the structure, function and pathology of the hippocampus and related cortical areas. It highlights the importance of the hippocampus in advancing many areas of modern neuroscience research. Written by experts in a wide range of disciplines, the second edition of The Hippocampus Book explores the interplay and corre...

Synthetic receptors that mediate antigen-dependent cell responses are transforming therapeutics, drug discovery and basic research1,2. However, established technologies such as chimeric antigen receptors³ can only detect immobilized antigens, have limited output scope and lack built-in drug control3, 4, 5, 6–7. Here we engineer synthetic G-protein-...

Memory consolidation assimilates recent experiences into long-term memory. This process requires the replay of learned sequences, although the content of these sequences remains controversial. Recent work has shown that the statistics of replay deviate from those of experience: stimuli that are experientially salient may be either recruited or supp...

While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell–...

Unverricht-Lundborg disease (ULD; EPM1) is an inherited neurodegenerative disorder characterized by onset at 6–15 years, stimulus-sensitive, action-activated myoclonus, epilepsy, and progressive neurological deterioration. It is caused by biallelic pathogenic variants in the CSTB gene, encoding a cystatin B. The most common of these is an unstable...

Targeted tissue ablation involving the anterior hippocampus is the standard of care for patients with drug-resistant mesial temporal lobe epilepsy. However, a substantial proportion continues to suffer from seizures even after surgery. We identified the fasciola cinereum (FC) neurons of the posterior hippocampal tail as an important seizure node in...

Visual place recognition (VPR) is the ability to recognize locations in a physical environment based only on visual inputs. It is a challenging task due to perceptual aliasing, viewpoint and appearance variations and complexity of dynamic scenes. Despite promising demonstrations, many state-of-the-art VPR approaches based on artificial neural netwo...

Distinct brain and behavioural states are associated with organized neural population dynamics that are thought to serve specific cognitive functions1, 2–3. Memory replay events, for example, occur during synchronous population events called sharp-wave ripples in the hippocampus while mice are in an ‘offline’ behavioural state, enabling cognitive m...

Endocannabinoid (eCB)–mediated suppression of inhibitory synapses has been hypothesized, but this has not yet been demonstrated to occur in vivo because of the difficulty in tracking eCB dynamics and synaptic plasticity during behavior. In mice navigating a linear track, we observed location-specific eCB signaling in hippocampal CA1 place cells, an...

Epilepsy is a prevalent disorder involving neuronal network hyperexcitability, yet existing therapeutic strategies often fail to provide optimal patient outcomes. Chemogenetic approaches, where exogenous receptors are expressed in defined brain areas and specifically activated by selective agonists, are appealing methods to constrain overactive neu...

Cephalopods are remarkable among invertebrates for their cognitive abilities, adaptive camouflage, novel structures, and propensity for recoding proteins through RNA editing. Due to the lack of genetically tractable cephalopod models, however, the mechanisms underlying these innovations are poorly understood. Genome editing tools such as CRISPR-Cas...

Epilepsy is a major disorder affecting millions of people. Although modern electrophysiological and imaging approaches provide high-resolution access to the multi-scale brain circuit malfunctions in epilepsy, our understanding of how behavior changes with epilepsy has remained rudimentary. As a result, screening for new therapies for children and a...

Technological advancements have facilitated the implementation of realistic, terrestrial-based complex 33-beam galactic cosmic radiation simulations (GCR Sim) to now probe central nervous system functionality. This work expands considerably on prior, simplified GCR simulations, yielding new insights into responses of male and female mice exposed to...

Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether pa...

Memory consolidation assimilates recent experiences into long-term memory. This process requires the replay of learned sequences, though the content of these sequences remains controversial. Recent work has shown that the statistics of replay deviate from those of experience: stimuli which are experientially salient may be either selected or suppre...

Decades of rodent research have established the role of hippocampal sharp wave ripples (SPW-Rs) in consolidating and guiding experience. More recently, intracranial recordings in humans have suggested their role in episodic and semantic memory. Yet, common standards for recording, detection, and reporting do not exist. Here, we outline the methodol...

The neurophysiology of cells and tissues are monitored electrophysiologically and optically in diverse experiments and species, ranging from flies to humans. Understanding the brain requires integration of data across this diversity, and thus these data must be findable, accessible, interoperable, and reusable (FAIR). This requires a standard langu...

During spatial exploration, neural circuits in the hippocampus store memories of sequences of sensory events encountered in the environment. When sensory information is absent during ‘offline’ resting periods, brief neuronal population bursts can ‘replay’ sequences of activity that resemble bouts of sensory experience. These sequences can occur in...

The convergence of advanced single‐cell in vivo functional imaging techniques, computational modelling tools and graph‐based network analytics has heralded new opportunities to study single‐cell dynamics across large‐scale networks, providing novel insights into principles of brain communication and pointing towards potential new strategies for tre...

Endocannabinoids (eCBs) are retrograde neuromodulators with important functions in a wide range of physiological processes, but their in vivo dynamics remain largely uncharacterized. Here we developed a genetically encoded eCB sensor called GRABeCB2.0. GRABeCB2.0 consists of a circular-permutated EGFP and the human CB1 cannabinoid receptor, providi...

Ripples are brief high-frequency electrographic events with important roles in episodic memory. However, the in vivo circuit mechanisms coordinating ripple-related activity among local and distant neuronal ensembles are not well understood. Here, we define key characteristics of a long-distance projecting GABAergic cell group in the mouse hippocamp...

Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. A remaining challenge is to combine high mechanical robustness with good electrical conduction, especially when patterned at small feature sizes. We...

Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. However, the grand challenge remains for the conducting polymer to possess both high mechanical ductility and good electrical conduction at cellular...

Locomotion-related signals in the brain To calculate where we are in space, continuous knowledge of one’ s speed is necessary. How does the brain know how fast the body is traveling during locomotion? Using in vivo calcium imaging, electrophysiology, optogenetics, cell tracing, and histology, Farrell et al . identified neurons in the rodent suprama...

Learning requires neural adaptations thought to be mediated by activity-dependent synaptic plasticity. A relatively non-standard form of synaptic plasticity driven by dendritic calcium spikes, or plateau potentials, has been reported to underlie place field formation in rodent hippocampal CA1 neurons. Here we found that this behavioral timescale sy...

Large-scale computational models of the brain are necessary to accurately represent anatomical and functional variability in neuronal biophysics across brain regions and also to capture and study local and global interactions between neuronal populations on a behaviorally-relevant temporal scale. We present the methodology behind and an initial imp...

Epileptic seizures are associated with excessive neuronal spiking. Perisomatic γ-aminobutyric acid (GABA)ergic interneurons specifically innervate the subcellular domains of postsynaptic excitatory cells that are critical for spike generation. With a revolution in transcriptomics-based cell taxonomy driving the development of novel transgenic mouse...

During spatial exploration, neural circuits in the hippocampus store memories of sequences of sensory events encountered in the environment. When sensory information is absent during "offline" resting periods, brief neuronal population bursts can "replay" sequences of activity that resemble bouts of sensory experience. These sequences can occur in...

The axon initial segment of hippocampal pyramidal cells is a key subcellular compartment for action potential generation, under GABAergic control by the “chandelier” or axo-axonic cells (AACs). Although AACs are the only cellular source of GABA targeting the initial segment, their in vivo activity patterns and influence over pyramidal cell dynamics...

A recognized risk of long-duration space travel arises from the elevated exposure astronauts face from galactic cosmic radiation (GCR), which is composed of a diverse array of energetic particles. There is now abundant evidence that exposures to many different charged particle GCR components within acute time frames are sufficient to induce central...

Neurological and psychiatric disorders are associated with pathological neural dynamics. The fundamental connectivity patterns of cell-cell communication networks that enable pathological dynamics to emerge remain unknown. Here, we studied epileptic circuits using a newly developed computational pipeline that leveraged single-cell calcium imaging o...

The brain’s endocannabinoid system is a powerful controller of neurotransmitter release, shaping synaptic communication under physiological and pathological conditions. However, our understanding of endocannabinoid signaling in vivo is limited by the inability to measure their changes at timescales commensurate with the high lability of lipid signa...

[This corrects the article DOI: 10.1016/j.isci.2021.102364.].

Biological cognition is based on the ability to autonomously acquire knowledge, or epistemic autonomy. Such self-supervision is largely absent in artificial neural networks (ANN) because they depend on externally set learning criteria. Yet training ANN using error backpropagation has created the current revolution in artificial intelligence, raisin...

The neurophysiology of cells and tissues are monitored electrophysiologically and optically in diverse experiments and species, ranging from flies to humans. Understanding the brain requires integration of data across this diversity, and thus these data must be findable, accessible, interoperable, and reusable (FAIR). This requires a standard langu...

The hippocampal formation displays a wide range of physiological responses to different spatial manipulations of the environment. However, very few attempts have been made to identify core computational principles underlying those hippocampal responses. Here, we capitalize on the observation that the entorhinal-hippocampal complex (EHC) forms a clo...

Achieving temporally precise, noninvasive control over specific neural cell types in the deep brain would advance the study of nervous system function. Here we use the potent channelrhodopsin ChRmine to achieve transcranial photoactivation of defined neural circuits, including midbrain and brainstem structures, at unprecedented depths of up to 7 mm...

Interneurons expressing cholecystokinin (CCK) and parvalbumin (PV) constitute two key GABAergic controllers of hippocampal pyramidal cell output. Although the temporally precise and millisecond-scale inhibitory regulation of neuronal ensembles delivered by PV interneurons is well established, the in vivo recruitment patterns of CCK-expressing baske...

Galactic cosmic radiation (GCR), composed of highly energetic and fully ionized atomic nuclei, can produce diverse deleterious effects on the body. In researching the neurological risks of GCR exposures, including during human spaceflight, various single-ion GCR irradiation paradigms have been shown to differentially disrupt cellular activity and o...

Significance Molecular reporters that “remember” the activity history of a cell and give a corresponding signal that can be read out by imaging, sequencing, or other modalities are valuable tools for the study of neural networks. Here, we develop a reporter that drives stable expression of any transgene (such as a fluorescent protein) in response t...

Several studies suggest that neurons from the lateral region of the SuM (SuML) innervating the dorsal dentate gyrus (DG) display a dual GABAergic and glutamatergic transmission and are specifically activated during paradoxical (REM) sleep (PS). The objective of the present study is to characterize the anatomical, neurochemical and electrophysiologi...

Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The reorganization of the dentate gyrus (DG) in TLE may create pathological conduction pathways for synchronous discharges in the temporal lobe, though critical microcircuit-level detail is missing from this pathophysiological intuition. In...

Neurological and psychiatric disorders are associated with pathological neural dynamics. The fundamental connectivity patterns of cell-cell communication networks that enable pathological dynamics to emerge remain unknown. Here, we studied epileptic circuits using a newly developed computational pipeline that leveraged single-cell calcium imaging o...

Endocannabinoids (eCBs) are retrograde neuromodulators that play an important role in a wide range of physiological processes; however, the release and in vivo dynamics of eCBs remain largely unknown, due in part to a lack of suitable probes capable of detecting eCBs with sufficient spatiotemporal resolution. Here, we developed a new eCB sensor cal...

Long-lasting confusion and memory difficulties during the postictal state remain a major unmet problem in epilepsy that lacks pathophysiological explanation and treatment. We previously identified that long-lasting periods of severe postictal hypoperfusion/hypoxia, not seizures per se, are associated with memory impairment after temporal lobe seizu...

Background: Cosmic radiation exposures have been found to elicit cognitive impairments involving a wide-range of underlying neuropathology including elevated oxidative stress, neural stem cell loss, and compromised neuronal architecture. Cognitive impairments have also been associated with sustained microglia activation following low dose exposure...

Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The dentate gyrus (DG) region of the hippocampal formation is highly reorganized in chronic TLE; in particular, pathological remodeling of the “dentate gate” is thought to open up pathological conduction pathways for synchronous discharges a...

Epilepsy is a neurological disorder characterized by recurrent seizures, where abnormal electrical activity begins in a local brain area and propagates before terminating. In a recent study, Liou and colleagues used multiscale computational modeling to gain mechanistic insights into clinical seizure dynamics based on cellular-level biophysical prop...

Radiotherapy, surgery and the chemotherapeutic agent temozolomide (TMZ) are frontline treatments for glioblastoma multiforme (GBM). However beneficial, GBM treatments nevertheless cause anxiety or depression in nearly 50% of patients. To further understand the basis of these neurological complications, we investigated the effects of combined radiot...

Objective To determine if closed‐loop optogenetic seizure intervention, previously shown to reduce seizure duration in a well‐established mouse model chronic temporal lobe epilepsy (TLE), also improves the associated comorbidity of impaired spatial memory. Methods Mice with chronic, spontaneous seizures in the unilateral intrahippocampal kainic ac...

According to standard models of synaptic plasticity, correlated activity between connected neurons drives changes in synaptic strengths to store associative memories. Here we tested this hypothesis in vivo by manipulating the activity of hippocampal place cells and measuring the resulting changes in spatial selectivity. We found that the spatial tu...

Long-lasting confusion and memory difficulties during the postictal state remain a major unmet problem in epilepsy that lacks pathophysiological explanation and treatment. Previously, we demonstrated that the postictal period is marked by a long-lasting stroke-like event in both animal models and humans with epilepsy (Farrell et al., 2016). Here, w...

Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, and is the most common form of adult epilepsy. In light of efforts spent characterizing this disease, effective treatments and a cure have remained elusive. TLE develops over a latent period that comprises structural and functional changes to the hippocampus (HPC) incl...

Epilepsy is a disorder caused by abnormalities at all levels of neural organization that often have complex and poorly understood interactions. Physiologically detailed computational models provide valuable tools for evaluation of possible clinical treatments of neural disorders because every parameter can be changed and many experimentally inacces...

Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, and is the most common form of adult epilepsy. In light of efforts spent characterizing this disease, effective treatments and a cure have remained elusive. TLE develops over a latent period that comprises structural and functional changes to the hippocampus (HPC) incl...

As NASA prepares for a mission to Mars, concerns regarding the health risks associated with deep space radiation exposure have emerged. Until now, the impacts of such exposures have only been studied in animals after acute exposures, using dose rates approximately 1.5E+05 higher than those actually encountered in space. Using a new, low dose rate n...

Throughout the brain, reciprocally connected excitatory and inhibitory neurons interact to produce gamma‐frequency oscillations. The emergent gamma rhythm synchronizes local neural activity and helps to select which cells should fire in each cycle. We previously found that such excitation‐inhibition microcircuits, however, have a potentially signif...

Several studies suggest that neurons from the lateral region of the SuM (SuML) innervating the dorsal dentate gyrus (DG) display a dual GABAergic and glutamatergic transmission and are specifically activated during paradoxical (REM) sleep (PS). The objective of the present study is to fully characterize the anatomical, neurochemical and electrophys...

Current drug treatments for epilepsy attempt to broadly restrict excitability to mask a symptom, seizures, with little regard for the heterogeneous mechanisms that underlie disease manifestation across individuals. Here, we discuss the need for a more complete view of epilepsy, outlining how key features at the cellular and microcircuit level can s...

Objective Temporal lobe epilepsy (TLE) is often associated with memory deficits. Reactivation of memory traces in the hippocampus occurs during sharp‐wave ripples (SWRs; 140‐250 Hz). To better understand the mechanisms underlying high‐frequency oscillations and cognitive comorbidities in epilepsy, we evaluated how rigorously identified deep CA1 pyr...

Neurodata Without Borders: Neurophysiology (NWB:N) is a data standard for neurophysiology, providing neuroscientists with a common standard to share, archive, use, and build common analysis tools for neurophysiology data. With NWB:N version 2.0 (NWB:N 2.0) we made significant advances towards creating a usable standard, software ecosystem, and vibr...

Neural stem cells (NSCs) in the adult mouse hippocampus occur in a specific neurogenic niche, where a multitude of extracellular signaling molecules converges to regulate NSC proliferation as well as fate and functional integration. However, the underlying mechanisms how NSCs react to extrinsic signals and convert them to intracellular responses st...

Hippocampal network operations supporting spatial navigation and declarative memory are traditionally interpreted in a framework where each hippocampal area, such as the dentate gyrus, CA3, and CA1, consists of homogeneous populations of functionally equivalent principal neurons. However, heterogeneity within hippocampal principal cell populations,...

Of the many perils associated with deep space travel to Mars, neurocognitive complications associated with cosmic radiation exposure are of particular concern. Despite these realizations, whether and how realistic doses of cosmic radiation cause cognitive deficits and neuronal circuitry alterations several months after exposure remains unclear. In...

A way to prevent generalized seizures? Temporal lobe epilepsy is the most common form of epilepsy in adults. Patients have spontaneous seizures and risk developing serious cognitive impairment. Bui et al. studied an animal model of temporal lobe epilepsy (see the Perspective by Scharfman). Selective optogenetic inhibition of dentate gyrus mossy cel...

The sparse single-spike activity of dentate gyrus granule cells (DG GCs) is punctuated by occasional brief bursts of 3–7 action potentials. It is well-known that such presynaptic bursts in individual mossy fibers (MFs; axons of granule cells) are often able to discharge postsynaptic CA3 pyramidal cells due to powerful short-term facilitation. Howev...

The advent of optogenetics has brought about an unprecedented ability to control neuronal activity with great spatial and temporal precision. Questions about neuronal circuitry that had previously been impossible or extremely difficult to test suddenly have become viable experimental questions. Although optogenetics was originally pioneered for use...

In silico computational neuroscience models of epileptiform activity and epilepsy-related alterations in brain circuits are constructed from mathematical equations that represent biophysical processes at different scales, from ion channels and synapses, to populations of neurons and large-scale networks encompassing entire brain regions. Computatio...

In this chapter, we review the development of biophysically detailed data-driven network models of the dentate gyrus that address clinically relevant structural alterations during epileptogenesis and their effects on network dynamics that potentially lead to hyperexcitability and pathological high frequency oscillations associated with epilepsy in...

See Lenck-Santini (doi:10.1093/awx205) for a scientific commentary on this article. Epileptic seizures represent altered neuronal network dynamics, but the temporal evolution and cellular substrates of the neuronal activity patterns associated with spontaneous seizures are not fully understood. We used simultaneous recordings from multiple neurons...

Epileptic seizures represent altered neuronal network dynamics, but the temporal evolution and cellular substrates of the neuronal activity patterns associated with spontaneous seizures are not fully understood. We used simultaneous recordings from multiple neurons in the hippocampus and neocortex of rats with chronic temporal lobe epilepsy to demo...

Local interneurons control principal cells within individual brain areas, but anecdotal observations indicate that interneuronal axons sometimes extend beyond strict anatomical boundaries. Here, we use the case of the dentate gyrus (DG) to show that boundary-crossing interneurons with cell bodies in CA3 and CA1 constitute a numerically significant...

The impact of dentate mossy cells on hippocampal activity remained uncertain despite a long history of investigation. In this issue of Neuron, Hashimotodani et al. (2017) discover a presynaptically expressed form of long-term potentiation at mossy cell outputs, shedding light on their mysterious function.

In the not too distant future, humankind will embark on one of its greatest adventures, the travel to distant planets. However, deep space travel is associated with an inevitable exposure to radiation fields. Space-relevant doses of protons elicit persistent disruptions in cognition and neuronal structure. However, whether space-relevant irradiatio...

Model sodium channel activation.The ion channel characterized in this figure was an Nav channel, inserted into a single compartment cell of diameter and length 16.8 microns (a soma) with a density such that the maximum, macroscopic conductance was 0.001 μS/cm2. The reversal potential of the channel was + 55 mV and the settings during the characteri...

Model PV+ basket cell current injection sweep.Simulated current injection sweep in AxoClamp ATF (tab-delimited) file format.DOI: http://dx.doi.org/10.7554/eLife.18566.014

Model pyramidal cell current injection sweep.Simulated current injection sweep in AxoClamp ATF (tab-delimited) file format.DOI: http://dx.doi.org/10.7554/eLife.18566.015

Model Schaffer Collateral-Associated cell current injection sweep.Simulated current injection sweep in AxoClamp ATF (tab-delimited) file format.DOI: http://dx.doi.org/10.7554/eLife.18566.016

Model paired recording of a Neurogliaform cell to Pyramidal cell connection.Simulated paired recordings where the postsynaptic cell was voltage-clamped at −50 mV and the reversal potential of the synapse was kept at its physiological potential, as defined in the network model code. Sodium channels in the postsynaptic cell were blocked to prevent a...

Model paired recording of a PV+ basket cell to Pyramidal cell connection.Simulated paired recordings where the postsynaptic cell was voltage-clamped at −50 mV and the reversal potential of the synapse was kept at its physiological potential, as defined in the network model code. Sodium channels in the postsynaptic cell were blocked to prevent a sup...

Model O-LM cell current injection sweep.Simulated current injection sweep in AxoClamp ATF (tab-delimited) file format.DOI: http://dx.doi.org/10.7554/eLife.18566.013

Model paired recording of a Bistratified cell to Pyramidal cell connection.Simulated paired recordings where the postsynaptic cell was voltage-clamped at −50 mV and the reversal potential of the synapse was kept at its physiological potential, as defined in the network model code. Sodium channels in the postsynaptic cell were blocked to prevent a s...

Model paired recording of a CA3 cell to Pyramidal cell connection.Simulated paired recordings where the postsynaptic cell was voltage-clamped at −50 mV and the reversal potential of the synapse was kept at its physiological potential, as defined in the network model code. Sodium channels in the postsynaptic cell were blocked to prevent a suprathres...

Model paired recording of a CCK+ basket cell to Pyramidal cell connection.Simulated paired recordings where the postsynaptic cell was voltage-clamped at −50 mV and the reversal potential of the synapse was kept at its physiological potential, as defined in the network model code. Sodium channels in the postsynaptic cell were blocked to prevent a su...