Extracellular Recordings Research Articles

Robust and memory-less median estimation for real-time spike detection.

We propose a novel 1-D median estimator specifically designed for the online detection of threshold-crossing signals, such as spikes in extracellular neural recordings. Compared to state-of-the-art algorithms, our method reduces estimator variance by up to eight times for a given buffer length. Likewise, for a given estimator variance, it requires a buffer length that is up to eight times smaller. This results in three significant advantages: the footprint area decreases by more than eight times, leading to reduced power consumption and a faster response to non-stationary signals.

Noisy neuronal populations effectively encode sound localization in the dorsal inferior colliculus of awake mice

Sound location coding has been extensively studied at the central nucleus of the mammalian inferior colliculus (CNIC), supporting a population code. However, this population code has not been extensively characterized on the single-trial level with simultaneous recordings or at other anatomical regions like the dorsal cortex of inferior colliculus (DCIC), which is relevant for learning-induced experience dependent plasticity. To address these knowledge gaps, here we made in two complementary ways large-scale recordings of DCIC populations from awake mice in response to sounds delivered from 13 different frontal horizontal locations (azimuths): volumetric two-photon calcium imaging with ~700 cells simultaneously recorded at a relatively low temporal resolution, and high-density single-unit extracellular recordings with ~20 cells simultaneously recorded at a high temporal resolution. Independent of the method, the recorded DCIC population responses revealed substantial trial-to-trial variation (neuronal noise) which was significantly correlated across pairs of neurons (noise correlations) in the passively listening condition. Nevertheless, decoding analysis supported that these noisy response patterns encode sound location on the single-trial basis, reaching errors that match the discrimination ability of mice. The detected noise correlations contributed to minimize the error of the DCIC population code of sound azimuth. Altogether these findings point out that DCIC can encode sound location in a similar format to what has been proposed for CNIC, opening exciting questions about how noise correlations could shape this code in the context of cortico-collicular input and experience-dependent plasticity.

Noisy neuronal populations effectively encode sound localization in the dorsal inferior colliculus of awake mice.

Sound location coding has been extensively studied at the central nucleus of the mammalian inferior colliculus (CNIC), supporting a population code. However, this population code has not been extensively characterized on the single-trial level with simultaneous recordings or at other anatomical regions like the dorsal cortex of inferior colliculus (DCIC), which is relevant for learning-induced experience dependent plasticity. To address these knowledge gaps, here we made in two complementary ways large-scale recordings of DCIC populations from awake mice in response to sounds delivered from 13 different frontal horizontal locations (azimuths): volumetric two-photon calcium imaging with ~700 cells simultaneously recorded at a relatively low temporal resolution, and high-density single-unit extracellular recordings with ~20 cells simultaneously recorded at a high temporal resolution. Independent of the method, the recorded DCIC population responses revealed substantial trial-to-trial variation (neuronal noise) which was significantly correlated across pairs of neurons (noise correlations) in the passively listening condition. Nevertheless, decoding analysis supported that these noisy response patterns encode sound location on the single-trial basis, reaching errors that match the discrimination ability of mice. The detected noise correlations contributed to minimize the error of the DCIC population code of sound azimuth. Altogether these findings point out that DCIC can encode sound location in a similar format to what has been proposed for CNIC, opening exciting questions about how noise correlations could shape this code in the context of cortico-collicular input and experience-dependent plasticity.

Context-dependent orientation discontinuity encoding by gamma rhythms in mouse primary visual cortex.

Through the modulation of its surround, an identical visual stimulus can be perceived as more or less salient, allowing it to either stand out or seamlessly integrate with the rest of the visual scene. Gamma rhythms are associated with processing stimulus features across extensive areas of the visual field. Consistent with this concept, the magnitude of visually induced gamma rhythm depends on how well stimulus features aligned both within and outside the classical receptive field (CRF) at the recording site. However, there still exists some uncertainty regarding the encoding of context-modulated orientation discontinuity by gamma rhythms. To address this concern, we conducted extracellular recordings in layers II/III and IV of area V1 using lightly anaesthetized mice to investigate the gamma tuning for stimuli with orientation discontinuity. Our study revealed that gamma rhythms exhibit a preference for stimuli with orientation discontinuity similar to the spiking responses observed in V1, which contradicts the findings of previous studies. Furthermore, the gamma tuning of discontinuous orientations exhibits a moderate correlation with spike tuning and a positive correlation with the strength of surround suppression. Therefore, our study suggests a close association between gamma tuning and nearby spiking tuning; additionally, it highlights the connection between the encoding of visual features by gamma rhythms and functional architecture, as well as neural signal integration. KEY POINTS: Visual context modulates the gamma rhythms in the primary visual cortex. Discontinuous orientation elicits significantly enhanced gamma rhythms compared to the iso-orientation stimulus. The gamma tuning of discontinuous orientations exhibits a moderate correlation with spike tuning. Gamma tuning of orientation discontinuity exhibits a positive correlation with the strength of surround suppression.

Methylone regulates fear memory and amygdala activity: A potential treatment for posttraumatic stress disorder?

Methylone (3,4-methylenedioxy-N-methylcathinone) is a rapid-acting entactogen that has demonstrated significant benefits for patients with post-traumatic stress disorder (PTSD) and exhibits good tolerability in phase 1 clinical trials. Despite these promising results, its preclinical effects on fear memory regulation and the underlying mechanisms remain largely unexplored. This study aims to investigate the impact of methylone on auditory fear extinction and its influence on neuronal and synaptic activity in the basolateral amygdala (BLA). Using C57BL/6 mice, we employed an auditory fear conditioning paradigm along with immunofluorescent staining, extracellular electrophysiological recording, and chemogenetic techniques. The results revealed that administering methylone at a dosage of 10 mg/kg, in conjunction with extinction trials, significantly decreased the retrieval of both recent and remote fear memories. Additionally, methylone effectively inhibited the renewal of remote fear memories and blocked spontaneous recovery. It also reduced fear generalization to both context and tone. At the cellular level, methylone increased c-fos expression in the BLA and induced sustained elevations in long-term potentiation and long-term depression at the synaptic level. Furthermore, intra-BLA microinfusion of methylone directly enhanced the extinction memory. Chemogenetic activation of the BLA mimicked the effects of methylone, whereas chemogenetic inhibition blocked them. These findings suggest that methylone modulates fear memories through its action on the BLA. This preclinical study offers a knowledge base and critical insights into the potential future application of methylone for PTSD treatment.

Naringenin Suppresses the Hyperexcitability of Trigeminal Nociceptive Neurons Associated with Inflammatory Hyperalgesia: Replacement of NSAIDs with Phytochemicals.

The present study examines whether the systemic application of naringenin (NRG) reduces inflammation-induced hyperexcitability in the spinal trigeminal nucleus caudalis (SpVc) related to hyperalgesia, and compares its impact with that of diclofenac (DIC). To provoke inflammation, the whisker pads of rats were injected with complete Freund's adjuvant, and subsequently, mechanical stimuli were administered to the orofacial region to determine the escape threshold. Compared to naïve rats, the inflamed rats showed a significantly lower mechanical threshold, and this reduced threshold returned to normal levels two days post-administration of NRG, DIC, and half-dose DIC plus half-dose NRG (1/2 DIC + 1/2 NRG). Using extracellular single-unit recordings, the activity of SpVc wide-dynamic range neurons was measured in response to mechanical stimulation of the orofacial area under anesthesia. The average firing rate of SpVc neurons when exposed to both non-painful and painful mechanical stimuli was significantly reduced in inflamed rats following NRG, DIC, and 1/2 DIC + 1/2 NRG administration. The heightened average spontaneous activity of SpVc neurons in rats with inflammation was significantly reduced following NRG, DIC, and 1/2 DIC + 1/2 NRG administration. The increased average receptive field size observed in inflamed rats reverted to normal levels after either NRG, DIC, or 1/2 DIC + 1/2 NRG treatment. These findings indicate that NRG administration can reduce inflammatory hyperalgesia linked to the heightened excitability of SpVc wide-dynamic range neurons.

Deep learning-based spike sorting: a survey.

Objective.Deep learning is increasingly permeating neuroscience, leading to a rise in signal-processing applications for extracellular recordings. These signals capture the activity of small neuronal populations, necessitating 'spike sorting' to assign action potentials (spikes) to their underlying neurons. With the rise in publications delving into new methodologies and techniques for deep learning-based spike sorting, it is crucial to synthesise these findings critically. This survey provides an in-depth evaluation of the approaches, methodologies and outcomes presented in recent articles, shedding light on the current state-of-the-art.Approach.Twenty-four articles published until December 2023 on deep learning-based spike sorting have been examined. The proposed methods are divided into three sub-problems of spike sorting: spike detection, feature extraction and classification. Moreover, integrated systems, i.e. models that detect spikes and extract features or do classification within a single network, are included.Main results.Although most algorithms have been developed for single-channel recordings, models utilising multi-channel data have already shown promising results, with efficient hardware implementations running quantised models on application-specific integrated circuits and field programmable gate arrays. Convolutional neural networks have been used extensively for spike detection and classification as the data can be processed spatiotemporally while maintaining low-parameter models and increasing generalisation and efficiency. Autoencoders have been mainly utilised for dimensionality reduction, enabling subsequent clustering with standard methods. Also, integrated systems have shown great potential in solving the spike sorting problem from end to end.Significance.This survey explores recent articles on deep learning-based spike sorting and highlights the capabilities of deep neural networks in overcoming associated challenges, but also highlights potential biases of certain models. Serving as a resource for both newcomers and seasoned researchers in the field, this work provides insights into the latest advancements and may inspire future model development.

Velocity coding in the central brain of bumblebees.

Moving animals experience wide-field optic flow due to the displacement of the retinal image during motion. These cues provide information about self-motion and are important for flight control and stabilization, and for more complex tasks like path integration. While in honeybees and bumblebees the use of wide-field optic flow in behavioral tasks is well investigated, little is known about the underlying neuronal processing of these cues. Furthermore, there is a discrepancy between the temporal frequency tuning observed in most motion-sensitive neurons described so far from the optic lobe of insects and the velocity tuning that has been shown for many behaviors. Here we investigated response properties of motion-sensitive neurons in the central brain of bumblebees. Extracellular recordings allowed us to present a large number of stimuli to probe the spatiotemporal tuning of these neurons. We presented moving gratings that simulated either front-to-back or back-to-front optic flow and found three response types. Direction-selective responses of one of the groups matched those of TN-neurons, which provide optic flow information to the central complex, while the other groups contained neurons with purely excitatory responses that were either selective or non-selective for stimulus direction. Most recorded units showed velocity-coding properties at lower angular velocities, but showed spatial frequency dependent responses at higher velocities. Based on behavioral data, neuronal modelling work has previously predicted the existence of non direction-selective neurons with such properties. Our data now provides physiological evidence for these neurons and shows that neurons with TN-like properties exhibit a similar velocity-dependent coding.

Pathological tau alters head direction signaling and induces spatial disorientation.

Disorientation is an early symptom of dementia, suggesting impairments in neural circuits responsible for head direction signaling. The anterodorsal thalamic nucleus (ADn) exhibits early and selective vulnerability to pathological misfolded forms of tau (ptau), a major hallmark of Alzheimer's disease and ageing. The ADn contains a high density of head direction (HD) cells; their disruption may contribute to spatial disorientation. To test this, we virally expressed human tau in the ADn of adult mice. HD-ptau mice were defined by ptau+ cells in the ADn and ptau+ axon terminals in postsynaptic target regions. Despite being able to learn spatial memory tasks, HD-ptau mice exhibited increased looping behavior during spatial learning and made a greater number of head turns during memory recall, consistent with disorientation. Using in vivo extracellular recordings, we identified ptau-expressing ADn cells and found that ADn cells from HD-ptau mice had reduced directionality and altered burst firing. These data suggest that ptau alters HD signaling, leading to impairments in spatial orientation.

Activation of 5-HT7 receptors in the mouse dentate gyrus does not affect theta-burst-induced plasticity at the perforant path synapse

BackgroundThe study examined the effects of 5-HT7 receptor activation on GABAergic transmission within the dentate gyrus and plasticity at the glutamatergic perforant path input.MethodsImmunofluorescence imaging was performed using transverse hippocampal slices from transgenic mice expressing green fluorescent protein (GFP) under the Htr7 promoter. This was followed by whole-cell patch clamp electrophysiological recordings assessing the effects of pharmacologically activating 5-HT7 receptors on spontaneous inhibitory postsynaptic currents recorded from dentate granule cells and hilar mossy cells—two glutamatergic neuron types present in the dentate gyrus. Extracellular recordings of field excitatory postsynaptic potentials were then performed to assess whether 5-HT7 receptor activation influenced theta-burst stimulation-evoked plasticity of the perforant path synaptic input.ResultsIt was found that parvalbumin and somatostatin interneurons in the dentate gyrus expressed GFP, which suggests they express 5-HT7 receptors. However, activation of 5-HT7 receptors had no effect on GABAergic transmission targeting mossy cells or granule cells. There was also no effect of 5-HT7 receptor activation on perforant path plasticity either with intact or blocked GABAA receptor signaling.ConclusionThe presence of 5-HT7 receptors in a subset of parvalbumin and somatostatin interneurons in the mouse dentate gyrus could mean that they are involved in the inhibitory control of dentate gyrus activity. However, this potential effect was not evident in slice recordings of inhibitory transmission targeting principal cells and did not affect perforant path plasticity. Further experiments are needed to fully elucidate the functional role of these receptors in the dentate gyrus.

Effects of lateral ventricle injection of 5,7-dihydroxytryptamine on neurons in the medial prefrontal cortex of rats: An electrophysiology study

The medial prefrontal cortex (mPFC) is closely associated with various psychopathologies in humans, and its dysfunction is invariably accompanied by abnormalities in the serotonin (5-hydroxytryptamine, 5-HT) system of the brain. In this study, in-vivo extracellular recording techniques were used to investigate changes in the excitability of pyramidal neurons and interneurons in the rat mPFC following injection of 5,7-dihydroxytryptamine (5,7-DHT) into the bilateral lateral ventricles to damage the serotoninergic neurons. The levels of 5-HT in the mPFC and dorsal raphe nucleus of rats were determined by high-performance liquid chromatography. The results showed that the levels of 5-HT were significantly reduced in the mPFC and dorsal raphe nucleus two weeks after injection of 5,7-DHT into the bilateral lateral ventricles, relative to the normal group. The discharge frequency of pyramidal neurons in the mPFC was markedly increased compared to the normal group, with a significant rise in burst discharge, while the average discharge frequency of interneurons was significantly reduced and tended towards irregular activity. The results of the study indicated that the brain’s 5-HT neurotransmitter system not only directly affects the activity of mPFC pyramidal neurons but also modulates the electrical activity of interneurons, thereby regulating the local microcircuitry within the mPFC and participating in its function.

Functional Adaptation in the Brain Habenulo-Mesencephalic Pathway During Cannabinoid Withdrawal.

The mesolimbic reward system originating from dopamine neurons in the ventral tegmental area (VTA) of the midbrain shows a profound reduction in function during cannabinoid withdrawal. This condition may underlie aversive states that lead to compulsive drug seeking and relapse. The lateral habenula (LHb) exerts negative control over the VTA via the GABA rostromedial tegmental nucleus (RMTg), representing a potential convergence point for drug-induced opponent processes. We hypothesized that the LHb-RMTg pathway might be causally involved in the hypodopaminergic state during cannabinoid withdrawal. To induce Δ9-tetrahydrocannabinol (THC) dependence, adult male Sprague-Dawley rats were treated with THC (15 mg/kg, i.p.) twice daily for 6.5-7 days. Administration of the cannabinoid antagonist rimonabant (5 mg/kg, i.p.) precipitated a robust behavioral withdrawal syndrome, while abrupt THC suspension caused milder signs of abstinence. Extracellular single unit recordings confirmed a marked decrease in the discharge frequency and burst firing of VTA dopamine neurons during THC withdrawal. The duration of RMTg-evoked inhibition was longer in THC withdrawn rats. Additionally, the spontaneous activity of RMTg neurons and of LHb neurons was strongly depressed during cannabinoid withdrawal. These findings support the hypothesis that functional changes in the habenulo-mesencephalic circuit are implicated in the mechanisms underlying substance use disorders.

Social and auditory experience shapes forebrain responsiveness in zebra finches before the sensitive period of vocal learning.

Early-life experiences with signals used in communication are instrumental in shaping an animal's social interactions. In songbirds, which use vocalizations for guiding social interactions and mate choice, recent studies show that sensory effects on development occur earlier than previously expected, even in embryos and nestlings. Here, we explored the neural dynamics underlying experience-dependent song categorization in young birds prior to the traditionally studied sensitive period of vocal learning that begins around 3 weeks post-hatch. We raised zebra finches either with their biological parents, cross-fostered by Bengalese finches beginning at embryonic day 9, or with only the non-singing mother from 2 days post-hatch. Then, 1-5 days after fledging, we conducted behavioral experiments and extracellular recordings in the auditory forebrain to test responses to zebra finch and Bengalese finch songs. Auditory forebrain neurons in cross-fostered and isolated birds showed increases in firing rate and decreases in responsiveness and selectivity. In cross-fostered birds, decreases in responsiveness and selectivity relative to white noise were specific to conspecific song stimuli, which paralleled behavioral attentiveness to conspecific songs in those same birds. This study shows that auditory and social experience can already impact song 'type' processing in the brains of nestlings, and that brain changes at this age can portend the effects of natal experience in adults.

Putative Nociceptive Responses in a Decapod Crustacean: The Shore Crab (Carcinus maenas).

Nociceptors are receptors that detect injurious stimuli and are necessary to convey such information from the periphery to the central nervous system. While nociception has been extensively studied in various taxa, there is relatively little electrophysiological evidence for the existence of nociceptors in decapod crustaceans. This study investigated putative nociceptive responses in the shore crabs, specifically their response to mechanical and noxious chemical stimuli. Extracellular multi-unit electrophysiological recordings were conducted from the anterior ganglion and the circumesophageal connective ganglia to assess nociceptive responses. Soft tissues at the joints of the chelae, antennae, and walking legs were stimulated using acetic acid (noxious stimulus) and von Frey hairs (mechanical stimulus), while nearby ganglion activity was recorded. The results indicate the existence of nociceptors in the tested areas, with mechanical stimuli eliciting shorter, more intense neural activity compared with acetic acid. Although acetic acid triggered responses in all areas, the antennae and antennules did not respond to mechanical stimuli. Though we acknowledge the challenges of conducting in vivo electrophysiological recordings, future research should focus on further characterizing nociceptor activity because the results suggest the presence of nociceptors.

Graphene Field‐Effect Transistors toward Study of Cardiac Ischemia at Early Stage

AbstractIschemia and reperfusion states are studied in a network of cardiomyocytes as a part of real‐state conditions of heart injuries and inflammations, specifically myocardial infractions. Arrays of graphene field‐effect transistors (GFETs) fabricated in this work are used for extracellular recordings of ischemia states of cardiac cells during the external triggering of the ischemia infarction. The low‐concentrated ischemic buffer solution allows to create a cell‐stress condition resulting in the reperfusion process. The results show that the action potentials recorded with the graphene transistors, especially their shape, and duration of the active segment in measured extracellular action potentials, can be used to characterize the real state of the studied cardiac cell culture. The unique property of GFETs to detect such small changes in the action potential of cells in cardiac healthy and unhealthy states provides prospects for building the next generation of ultrasensitive biosensors, enabling the detection of acute ischemic states at an early stage.

A new function of offset response in the primate auditory cortex: marker of temporal integration

Offset responses are traditionally viewed as indicators of sound cessation. Here, we investigate offset responses to auditory click trains, examining how they are modulated by inter-click intervals (ICIs) and train duration. Using extracellular recordings and electrocorticography (ECoG) in non-human primates, alongside electroencephalography (EEG) in humans, we show that offset responses are significantly influenced by both ICI and train length, thereby establishing them as markers of temporal integration. We introduce the concept of the ‘Neuronal Integrative Window’ (NIW), defined as the temporal span during which neurons integrate stimuli to produce or modulate the temporal integration signal. Our data reveal that on the neuronal level, the auditory cortex (AC) exhibits a more expansive NIW than the medial geniculate body (MGB), integrating stimuli over longer durations and showing a preference for larger ICIs. Furthermore, our results indicate that offset responses could serve as potential biomarkers for neurological and psychiatric conditions, highlighted by their sensitivity to pharmacological modulation with ketamine. This study advances our understanding of auditory temporal processing and proposes a novel approach for assessing and monitoring brain health.

Chronic recording of brain activity in awake toads.

Amphibians represent an important evolutionary transition from aquatic to terrestrial environments and they display a large variety of complex behaviors despite a relatively simple brain. However, their brain activity is not as well characterized as that of many other vertebrates, partially due to physiological traits that have made electrophysiology recordings difficult to perform in awake and moving animals. We implanted flexible mesh electronics in the cane toad (Rhinella marina) and performed extracellular recordings in the telencephalon of anesthetized toads and partially restrained, awake toads over multiple days. We recorded brain activity over five consecutive days in awake toads and over a 15 week period in a toad that was anesthetized during recordings. We were able to perform spike sorting and identified single- and multi-unit activity in all toads. To our knowledge, this is the first report of a modern method to perform electrophysiology in non-paralyzed toads over multiple days, though there are historical references to short term recordings in the past. Implementing flexible mesh electronics in amphibian species will allow for advanced studies of the neural basis of amphibian behaviors.

Visual exposure to green light therapy reduces knee joint pain and alters the lipidome in osteoarthritic rats.

Visual exposure to dim, green, light has been found to reduce pain levels in patients living with migraine, low back pain, and fibromyalgia. Preclinical studies discovered that the analgesic effect of green light was due to the central release of endogenous opioids and a reduction in inflammatory cytokines in the cerebrospinal fluid. The present study assessed the effect of green light therapy (GLT) on joint pain in a rat model of osteoarthritis (OA) and investigated the role of endolipids. Male and female Wistar rats (207-318 g) received an intra-articular injection of sodium monoiodoacetate (3 mg in 50 μL saline) into the knee to induce OA. On day 9, animals were placed in a room illuminated by either white (neutral-white 4000K; 20 lux) or green (wavelength: 525 nm; luminance: 20 lux) light for 5 days (8 hours per day). Joint nociception was assessed by von Frey hair algesiometry, dynamic weight bearing, and in vivo single unit extracellular recordings from knee joint mechanonociceptors. Compared to white light, GLT significantly reduced secondary mechanical hypersensitivity in both sexes and improved hindlimb weight bearing in females only. There was no effect of GLT on joint nociceptor activity in either sex. Serum lipidomics indicated an increase in circulating analgesic endolipids in response to GLT, particularly the N-acyl-glycines. Partial blockade of the endocannabinoid system with the G protein receptor-18/cannabinoid-1 receptor antagonist AM281 (500 μg/kg i.p.) attenuated GLT-induced analgesia. These data show for the first time that GLT acts to reduce OA pain by upregulating circulating analgesic endolipids, which then engage the endocannabinoid system.

Assembloid model to study loop circuits of the human nervous system.

Neural circuits connecting the cerebral cortex, the basal ganglia and the thalamus are fundamental networks for sensorimotor processing and their dysfunction has been consistently implicated in neuropsychiatric disorders 1-9 . These recursive, loop circuits have been investigated in animal models and by clinical neuroimaging, however, direct functional access to developing human neurons forming these networks has been limited. Here, we use human pluripotent stem cells to reconstruct an in vitro cortico-striatal-thalamic-cortical circuit by creating a four-part loop assembloid. More specifically, we generate regionalized neural organoids that resemble the key elements of the cortico-striatal-thalamic-cortical circuit, and functionally integrate them into loop assembloids using custom 3D-printed biocompatible wells. Volumetric and mesoscale calcium imaging, as well as extracellular recordings from individual parts of these assembloids reveal the emergence of synchronized patterns of neuronal activity. In addition, a multi-step rabies retrograde tracing approach demonstrate the formation of neuronal connectivity across the network in loop assembloids. Lastly, we apply this system to study heterozygous loss of ASH1L gene associated with autism spectrum disorder and Tourette syndrome and discover aberrant synchronized activity in disease model assembloids. Taken together, this human multi-cellular platform will facilitate functional investigations of the cortico-striatal-thalamic-cortical circuit in the context of early human development and in disease conditions.

Comparison of extracellular Giant depolarizing potentials in vitro and early sharp waves in vivo in the CA1 hippocampus of neonatal rats

Giant Depolarizing Potentials (GDPs) and Early Sharp Waves (eSPWs) are the major patterns of neuronal network activity in the developing hippocampus of neonatal rodents in vitro and in vivo, respectively. Because of certain similarities in their electrographic traits, GDPs and eSPWs were originally considered as homologous patterns. Here, we compared electrographic features and current density profiles of field GDPs (fGDPs) and eSPWs using extracellular multisite silicon probe recordings from neonatal rat CA1 hippocampus. We found that fGDPs in hippocampal slices were much less in amplitude than eSPWs, and were characterized by electronegativity and current sinks in CA1 pyramidal cell layer and stratum radiatum, and positive waves/sources in stratum lacunosum-moleculare. eSPWs in vivo showed a remarkably different depth profile, with positivity and current source in the CA1 pyramidal cell layer, and negativity/sinks in stratum radiatum and stratum lacunosum-moleculare. Current sinks of CA3-evoked responses corresponded to sinks of fGDPs and eSPWs in the stratum radiatum. However, current sinks of entorhinal inputs - evoked responses in stratum lacunosum-moleculare, which were characteristic of eSPWs, were absent in fGDPs. In addition, fGDPs more strongly modulated neuronal firing in CA1 compared to eSPWs. Thus, we show important differences in the electrographic properties of GDPs and eSPWs that challenge the homology of these two activity patterns.