Majority Of Neurons Research Articles

3D directional tuning in the orofacial sensorimotor cortex during natural feeding and drinking.

Directional tongue movements are essential for vital behaviors, such as feeding and speech, to position food for chewing and swallowing safely and to position the tongue for accurate sound production. While directional tuning has been well-studied in the arm region of the sensorimotor cortex during reaching tasks, little is known about how 3D tongue direction is encoded in the orofacial region during natural behaviors. Understanding how tongue direction is represented in the brain has important implications for improving rehabilitation for people with orolingual dysfunctions. The goal of this study is to investigate how 3D direction of tongue movement is encoded in the orofacial sensorimotor cortex (OSMCx) during feeding and drinking, and how this process is affected by the loss of oral sensation. Using biplanar video-radiography to track implanted markers in the tongue of behaving non-human primates (Macaca mulatta), 3D positional data was recorded simultaneously with spiking activity in primary motor (MIo) and somatosensory (SIo) areas of the orofacial cortex using chronically implanted microelectrode arrays. In some sessions, tasks were preceded by bilateral nerve block injections to the sensory branches of the trigeminal nerve. Modulation to the 3D tongue direction was found in a majority of MIo but not SIo neurons during feeding, while the majority of neurons in both areas were modulated to the direction of tongue protrusion during drinking. Following sensory loss, the proportion of directionally tuned neurons decreased and shifts in the distribution of preferred direction were observed in OSMCx neurons. Overall, we show that 3D directional tuning of MIo and SIo to tongue movements varies with behavioral tasks and availability of sensory information.

Hyperpolarization-activated currents drive neuronal activation sequences in sleep

Sequential neuronal patterns are believed to support information processing in the cortex, yet their origin is still a matter of debate. We report that neuronal activity in the mouse postsubiculum (PoSub), where a majority of neurons are modulated by the animal's head direction, was sequentially activated along the dorsoventral axis during sleep at the transition from hyperpolarized "DOWN" to activated "UP" states, while representing a stable direction. Computational modeling suggested that these dynamics could be attributed to a spatial gradient of hyperpolarization-activated currents (Ih), which we confirmed in exvivo slice experiments and corroborated in other cortical structures. These findings open up the possibility that varying amounts of Ih across cortical neurons could result in sequential neuronal patterns and that traveling activity upstream of the entorhinal-hippocampal circuit organizes large-scale neuronal activity supporting learning and memory during sleep.

Role of Aluminium in Alzheimer’s disease: Ultrastructural Study in Rat Hippocampus

Background: Exposure to high levels of aluminium (Al) leads to neurotoxicity. Hippocampus is one of the preferred sites of aluminium accumulation. Nevertheless, the role of Al in Alzheimer’s disease (AD) remains controversial and there is little proof directly interlinking Al to AD. Aims: The present study was undertaken to find out the occurrence of AD pathogenesis in Hippocampus under moderate aluminium exposure in rats. Materials and Methods: Adult rats were divided into control (C) and aluminium treated (E) groups having eight animal each. The rats in group E were exposed to aluminium 4.2 mg/kg body weight for three months with due approval from Institute Animal Ethics Committee. The hippocampus was processed for histopathological and electron microscopy observation. Results: Moderate Al intake produces significant reduction in the count of Pyramidal cells in hippocampus identified by shrunken cells as well as pyknosis in cell bodies. The differences between the cell numbers in all groups were found to be statistically significant (P  0.05). Cornu Ammonis (CA) exhibited significantly reduced nissl bodies with a marked reduction in neuronal cell loss. Neurofibrillary tangle and plaques were not seen in the given dose of Al exposure. Electron microscopy from experimental group showed that the majority of neurons were disintegrating, the nuclear membrane has ruptured, and nucleoli appeared significantly distorted. The chromatin condensed and the mitochondria had disintegrated. Many vacuoles and lipofuscin sediment in cytoplasm, as compared to the control group noted. Conclusion: Present data demonstrated that moderate chronic aluminium exposure 4.2mg/kg body weight induced neurodegeneration in hippocampus but not significant for Alzheimer’s disease pathogenesis. KEYWORDS: Aluminium, Hippocampus, Alzheimer’s Disease, Neurodegeneration, Histopathology, Electron microscopy.

Somatic and terminal CB1 receptors are differentially coupled to voltage-gated sodium channels in neocortical neurons

Endogenous cannabinoid signaling is vital for important brain functions, and the same pathways can be modified pharmacologically to treat pain, epilepsy, and posttraumatic stress disorder. Endocannabinoid-mediated changes to excitability are predominantly attributed to 2-arachidonoylglycerol (2-AG) acting presynaptically via the canonical cannabinoid receptor, CB1. Here, we identify a mechanism in the neocortex by which anandamide (AEA), another major endocannabinoid, but not 2-AG, powerfully inhibits somatically recorded voltage-gated sodium channel (VGSC) currents in the majority of neurons. This pathway involves intracellular CB1 that, when activated by anandamide, decreases the likelihood of recurrent action potential generation. WIN 55,212-2 similarly activates CB1 and inhibits VGSC currents, indicating that this pathway is also positioned to mediate the actions of exogenous cannabinoids on neuronal excitability. The coupling between CB1 and VGSCs is absent at nerve terminals, and 2-AG does not block somatic VGSC currents, indicating functional compartmentalization of the actions of two endocannabinoids.

Nucleus accumbens shell modulates seizure propagation in a mouse temporal lobe epilepsy model.

Temporal lobe epilepsy (TLE) is the most common form of epilepsy with focal seizures which in some conditions can develop into secondarily generalized tonic-clonic seizures by the propagation of epileptic activities in the temporal lobe to other brain areas. The nucleus accumbens (NAc) has been suggested as a treatment target for TLE as accumulating evidence indicates that the NAc, especially its shell, participates in the process of epileptic seizures of patients and animal models with TLE. The majority of neurons in the NAc are GABAergic medium spiny neurons (MSNs) expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). However, the direct evidence of the NAc shell participating in the propagation of TLE seizures is missing, and its cell type-specific modulatory roles in TLE seizures are unknown. In this study, we microinjected kainic acid into basolateral amygdala (BLA) to make a mouse model of TLE with initial focal seizures and secondarily generalized seizures (SGSs). We found that TLE seizures caused robust c-fos expression in the NAc shell and increased neuronal excitability of D1R-expressing MSN (D1R-MSN) and D2R-expressing MSN (D2R-MSN). Pharmacological inhibition of the NAc shell alleviated TLE seizures by reducing the number of SGSs and seizure stages. Cell-type-specific chemogenetic inhibition of either D1R-MSN or D2R-MSN showed similar effects with pharmacological inhibition of the NAc shell. Both pharmacological and cell-type-specific chemogenetic inhibition of the NAc shell did not alter the onset time of focal seizures. Collectively, these findings indicate that the NAc shell and its D1R-MSN or D2R-MSN mainly participate in the propagation and generalization of the TLE seizures.

Bayesian connective field modeling using a Markov Chain Monte Carlo approach

The majority of neurons in the human brain process signals from neurons elsewhere in the brain.Connective Field (CF) modelling is a biologically-grounded method to describe this essential aspect of the brain's circuitry. It allows characterizing the response of a population of neurons in terms of the activity in another part of the brain. CF modelling translates the concept of the receptive field (RF) into the domain of connectivity by assessing, at the voxel level, the spatial dependency between signals in distinct cortical visual field areas. Thus, the approach enables to characterize the functional cortical circuitry of the human cortex. While already very useful, the present CF modelling approach has some intrinsic limitations due to the fact that it only estimates the model's explained variance and not the probability distribution associated with the estimated parameters. If we could resolve this, CF modelling would lend itself much better for statistical comparisons at the level of single voxels and individuals. This is important when trying to gain a detailed understanding of the neurobiology and pathophysiology of the visual cortex, notably in rare cases. To enable this, we present a Bayesian approach to CF modeling (bCF). Using a Markov Chain Monte Carlo (MCMC) procedure, it estimates the posterior probability distribution underlying the CF parameters. Based on this, bCF quantifies, at the voxel level, the uncertainty associated with each parameter estimate. This information can be used in various ways to increase confidence in the CF model predictions. We applied bCF to BOLD responses recorded in the early human visual cortex using 3T fMRI. We estimated both the CF parameters and their associated uncertainties and show they are only weakly correlated. Moreover, we show how bCF facilitates the use of effect size (beta) as a data-driven parameter that can be used to select the most reliable voxels for further analysis. Finally, to further illustrate the functionality gained by bCF, we apply it to perform a voxel-level comparison of a single, circular symmetric, Gaussian versus a Difference-of-Gaussian model. We conclude that our bCF framework provides a comprehensive tool to study human functional cortical circuitry in health and disease.

In Vivo Photometry Reveals Insulin and 2-Deoxyglucose Maintain Prolonged Inhibition of VMH Vglut2 Neurons in Male Mice.

The ventromedial hypothalamic (VMH) nucleus is a well-established hub for energy and glucose homeostasis. In particular, VMH neurons are thought to be important for initiating the counterregulatory response to hypoglycemia, and ex vivo electrophysiology and immunohistochemistry data indicate a clear role for VMH neurons in sensing glucose concentration. However, the temporal response of VMH neurons to physiologically relevant changes in glucose availability in vivo has been hampered by a lack of available tools for measuring neuronal activity over time. Since the majority of neurons within the VMH are glutamatergic and can be targeted using the vesicular glutamate transporter Vglut2, we expressed cre-dependent GCaMP7s in Vglut2 cre mice and examined the response profile of VMH to intraperitoneal injections of glucose, insulin, and 2-deoxyglucose (2DG). We show that reduced available glucose via insulin-induced hypoglycemia and 2DG-induced glucoprivation, but not hyperglycemia induced by glucose injection, inhibits VMH Vglut2 neuronal population activity in vivo. Surprisingly, this inhibition was maintained for at least 45 minutes despite prolonged hypoglycemia and initiation of a counterregulatory response. Thus, although VMH stimulation, via pharmacological, electrical, or optogenetic approaches, is sufficient to drive a counterregulatory response, our data suggest VMH Vglut2 neurons are not the main drivers required to do so, since VMH Vglut2 neuronal population activity remains suppressed during hypoglycemia and glucoprivation.

Effects of involuntary treadmill running in combination with swimming on adult neurogenesis in an Alzheimer's mouse model

Physical exercise plays a role on the prevention and treatment of Alzheimer's disease (AD), but the exercise mode and the mechanism for these positive effects is still ambiguous. Here, we investigated the effect of an aerobic interval exercise, running in combination with swimming, on behavioral dysfunction and associated adult neurogenesis in a mouse model of AD. We demonstrate that 4 weeks of the exercise could ameliorate Aβ42 oligomer-induced cognitive impairment in mice utilizing Morris water maze tests. Additionally, the exercised Aβ42 oligomer-induced mice exhibited a significant reduction of anxiety- and depression-like behaviors compared to the sedentary Aβ42 oligomer-induced mice utilizing an Elevated zero maze and a Tail suspension test. Moreover, by utilizing 5′-bromodeoxyuridine (BrdU) as an exogenous cell tracer, we found that the exercised Aβ42 oligomer-induced mice displayed a significant increase in newborn cells (BrdU+ cells), which differentiated into a majority of neurons (BrdU+ DCX+ cells or BrdU+NeuN+ cells) and a few of astrocytes (BrdU+GFAP+ cells). Likewise, the exercised Aβ42 oligomer-induced mice also displayed the higher levels of NeuN, PSD95, synaptophysin, Bcl-2 and lower level of GFAP protein. Furthermore, alteration of serum metabolites in transgenic AD mice between the exercised and sedentary group were significantly associated with lipid metabolism, amino acid metabolism, and neurotransmitters. These findings suggest that combined aerobic interval exercise-mediated metabolites and proteins contributed to improving adult neurogenesis and behavioral performance after AD pathology, which might provide a promising therapeutic strategy for AD.

Differential Serotonergic Modulation of Principal Neurons and Interneurons in the Anterior Piriform Cortex.

Originating from the brainstem raphe nuclei, serotonin is an important neuromodulator involved in a variety of physiological and pathological functions. Specific optogenetic stimulation of serotonergic neurons results in the divisive suppression of spontaneous, but not sensory evoked activity in the majority of neurons in the primary olfactory cortex and an increase in firing in a minority of neurons. To reveal the mechanisms involved in this dual serotonergic control of cortical activity we used a combination of in vitro electrophysiological recordings from identified neurons in the primary olfactory cortex, optogenetics and pharmacology and found that serotonin suppressed the activity of principal neurons, but excited local interneurons. The results have important implications in sensory information processing and other functions of the olfactory cortex and related brain areas.

Novel stimuli evoke excess activity in the mouse primary visual cortex

To explore how neural circuits represent novel versus familiar inputs, we presented mice with repeated sets of images with novel images sparsely substituted. Using two-photon calcium imaging to record from layer 2/3 neurons in the mouse primary visual cortex, we found that novel images evoked excess activity in the majority of neurons. This novelty response rapidly emerged, arising with a time constant of 2.6 ± 0.9 s. When a new image set was repeatedly presented, a majority of neurons had similarly elevated activity for the first few presentations, which decayed to steady state with a time constant of 1.4 ± 0.4 s. When we increased the number of images in the set, the novelty response's amplitude decreased, defining a capacity to store ∼15 familiar images under our conditions. These results could be explained quantitatively using an adaptive subunit model in which presynaptic neurons have individual tuning and gain control. This result shows that local neural circuits can create different representations for novel versus familiar inputs using generic, widely available mechanisms.

Spinal Cord Injury Significantly Alters the Properties of Reticulospinal Neurons: I. Biophysical Properties, Firing Patterns, Excitability, and Synaptic Inputs.

Following spinal cord injury (SCI) for larval lampreys, descending axons of reticulospinal (RS) neurons regenerate, and locomotor function gradually recovers. In the present study, the electrophysiological properties of uninjured (left)-injured (right) pairs of large, identified RS neurons were compared following rostral, right spinal cord hemi-transections (HTs). First, changes in firing patterns of injured RS neurons began in as little as 2–3 days following injury, these changes were maximal at ~2–3 weeks (wks), and by 12–16 wks normal firing patterns were restored for the majority of neurons. Second, at ~2–3 wks following spinal cord HTs, injured RS neurons displayed several significant changes in properties compared to uninjured neurons: (a) more hyperpolarized VREST; (b) longer membrane time constant and larger membrane capacitance; (c) increased voltage and current thresholds for action potentials (APs); (d) larger amplitudes and durations for APs; (e) higher slope for the repolarizing phase of APs; (f) virtual absence of some afterpotential components, including the slow afterhyperpolarization (sAHP); (g) altered, injury-type firing patterns; and (h) reduced average and peak firing (spiking) frequencies during applied depolarizing currents. These altered properties, referred to as the “injury phenotype”, reduced excitability and spiking frequencies of injured RS neurons compared to uninjured neurons. Third, artificially injecting a current to add a sAHP waveform following APs for injured neurons or removing the sAHP following APs for uninjured neurons did not convert these neurons to normal firing patterns or injury-type firing patterns, respectively. Fourth, trigeminal sensory-evoked synaptic responses recorded from uninjured and injured pairs of RS neurons were not significantly different. Following SCI, injured lamprey RS neurons displayed several dramatic changes in their biophysical properties that are expected to reduce calcium influx and provide supportive intracellular conditions for axonal regeneration.

Micro-electrode Recordings in Stereotactic Functional Neurosurgery

Accurate targeting to the sensorimotor territory of the globus pallidus internus (GPi), the subthalamic nucleus (STN), and the thalamic ventral intermediate nucleus (Vim) is crucial for the stereotactic neurosurgery of lesioning or implantation of a deep brain stimulation electrode. Intra-operative micro-electrode recording can aid in the localization of these structures. Neurons in the GPi are characterized by high-frequency tonic discharge. The STN has a high density of neurons that show irregular discharge. The majority of neurons in the sensorimotor territory of the GPi and STN exhibit neuronal responses to passive manipulation or active movement of the limbs and orofacial parts, and they are somatotopically arranged. Neurons responding to movements of the legs, arms, and face were found along the dorsal-ventral axis in the posterolateral GPi and along the medial-lateral axis in the posterolateral STN. Similarly, in the lateral part of the thalamic Vim nucleus, most neurons exhibit kinesthetic responses that show well-organized somatotopic arrangement, with the leg on the dorsolateral side, arm on the medioventral side, and face on the more medial side. Some Vim neurons have rhythmic bursting discharges synchronous with limb tremor. These electrophysiological findings allow us to achieve better surgical results.

A quick and versatile protocol for the 3D visualization of transgene expression across the whole body of larval Drosophila

Larval Drosophila are used as a genetically accessible study case in many areas of biological research. Here we report a fast, robust and user-friendly procedure for the whole-body multi-fluorescence imaging of Drosophila larvae; the protocol has been optimized specifically for larvae by systematically tackling the pitfalls associated with clearing this small but cuticularized organism. Tests on various fluorescent proteins reveal that the recently introduced monomeric infrared fluorescent protein (mIFP) is particularly suitable for our approach. This approach comprises an effective, low-cost clearing protocol with minimal handling time and reduced toxicity in the reagents employed. It combines a success rate high enough to allow for small-scale screening approaches and a resolution sufficient for cellular-level analyses with light sheet and confocal microscopy. Given that publications and database documentations typically specify expression patterns of transgenic driver lines only within a given organ system of interest, the present procedure should be versatile enough to extend such documentation systematically to the whole body. As examples, the expression patterns of transgenic driver lines covering the majority of neurons, or subsets of chemosensory, central brain or motor neurons, are documented in the context of whole larval body volumes (using nsyb-Gal4, IR76b-Gal4, APL-Gal4 and mushroom body Kenyon cells, or OK371-Gal4, respectively). Notably, the presented protocol allows for triple-color fluorescence imaging with near-infrared, red and yellow fluorescent proteins.

Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons.

Primary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured rat neocortical pyramidal neurons and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to excitatory neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

Changes in the Expression of Steroidogenic Factor 1 (SF-1) in Neurons in the Ventromedial Nucleus of the Hypothalamus in Rats on Aging

Expression of steroidogenic factor 1 in neurons in the ventromedial nucleus of the hypothalamus in rats was studied using an immunohistochemical method and western blotting in young (2–3 months) and aged (2–2.5 years) male and female rats. Steroidogenic factor 1 was present in a majority of neurons in the ventromedial nucleus of the hypothalamus in young and aged rats, in the dorsomedial part of the nucleus. In aged rats, the proportion of neurons immunoreactive to steroidogenic factor 1 decreased significantly, from 88% to 68% in males and from 82 to 66% in females. There were no significant sex-related differences in the numbers of immunopositive neurons in either age group. Expression of steroidogenic factor 1 was also significantly lower in aged male and female rats in terms of western blot results. Thus, aging was associated with changes in the neurochemical composition of the ventromedial nucleus of the hypothalamus, which is involved in regulating energy metabolism and sexual behavior.

The convergence of aversion and reward signals in individual neurons of the mice lateral habenula

The lateral habenula (LHb) and ventral tegmental area (VTA) are two structures closely connected, and they serve as aversion and reward junction of the brain, respectively. This study investigated whether single neurons in the LHb/VTA respond to both aversion and reward stimuli and how these neurons regulate aversion and reward processing. Using optogenetic combined with multi-channel recording of LHb / VTA neuronal discharge, we found that most single neurons in the LHb/ VTA respond to both aversion and reward stimuli. Interestingly, majority of neurons in LHb were aversion-activated and reward-inhibited neurons, consisting mainly of glutamatergic neurons, while most neurons in VTA were reward-activated and aversion-inhibited neurons, which inhibited by glutamatergic neurons in the LHb. Furthermore, optogenetic activation or inhibition of glutamatergic neurons in LHb and their terminals in VTA could induce aversive or reward behaviors. These results indicate that identical neurons in the LHb and VTA have different responses to reward and aversion stimuli. The aversion behaviors induced by activating LHb glutamatergic neurons may be due to its inhibition on reward-activated neurons in VTA. This study suggests that interplay between the LHb and VTA neurons may play a key role in regulating reward and aversion behaviors.

Choice-dependent cross-modal interaction in the medial prefrontal cortex of rats

Cross-modal interaction (CMI) could significantly influence the perceptional or decision-making process in many circumstances. However, it remains poorly understood what integrative strategies are employed by the brain to deal with different task contexts. To explore it, we examined neural activities of the medial prefrontal cortex (mPFC) of rats performing cue-guided two-alternative forced-choice tasks. In a task requiring rats to discriminate stimuli based on auditory cue, the simultaneous presentation of an uninformative visual cue substantially strengthened mPFC neurons' capability of auditory discrimination mainly through enhancing the response to the preferred cue. Doing this also increased the number of neurons revealing a cue preference. If the task was changed slightly and a visual cue, like the auditory, denoted a specific behavioral direction, mPFC neurons frequently showed a different CMI pattern with an effect of cross-modal enhancement best evoked in information-congruent multisensory trials. In a choice free task, however, the majority of neurons failed to show a cross-modal enhancement effect and cue preference. These results indicate that CMI at the neuronal level is context-dependent in a way that differs from what has been shown in previous studies.

UV-Induced Neuronal Degeneration in the Rat Cerebral Cortex.

Irradiation with ultraviolet (UV) light on the cortical surface can induce a focal brain lesion (UV lesion) in rodents. In the present study, we investigated the process of establishing a UV lesion. Rats underwent UV irradiation (365-nm wavelength, 2.0 mWh) over the dura, and time-dependent changes in the cortical tissue were analyzed histologically. We found that the majority of neurons in the lesion started to degenerate within 24 h and the rest disappeared within 5 days after irradiation. UV-induced neuronal degeneration progressed in a layer-dependent manner. Moreover, UV-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity and heme oxygenase-1 (HO-1) immunoreactivity were also detected. These findings suggest that UV irradiation in the brain can induce gradual neural degeneration and oxidative stress. Importantly, UV vulnerability may vary among cortical layers. UV-induced cell death may be due to apoptosis; however, there remains a possibility that UV-irradiated cells were degenerated via processes other than apoptosis. The UV lesion technique will not only assist in investigating brain function at a targeted site but may also serve as a pathophysiological model of focal brain injury and/or neurodegenerative disorders.

Direction-selective motion discrimination by traveling waves in visual cortex.

The majority of neurons in primary visual cortex respond selectively to bars of light that have a specific orientation and move in a specific direction. The spatial and temporal responses of such neurons are non-separable. How neurons accomplish that computational feat without resort to explicit time delays is unknown. We propose a novel neural mechanism whereby visual cortex computes non-separable responses by generating endogenous traveling waves of neural activity that resonate with the space-time signature of the visual stimulus. The spatiotemporal characteristics of the response are defined by the local topology of excitatory and inhibitory lateral connections in the cortex. We simulated the interaction between endogenous traveling waves and the visual stimulus using spatially distributed populations of excitatory and inhibitory neurons with Wilson-Cowan dynamics and inhibitory-surround coupling. Our model reliably detected visual gratings that moved with a given speed and direction provided that we incorporated neural competition to suppress false motion signals in the opposite direction. The findings suggest that endogenous traveling waves in visual cortex can impart direction-selectivity on neural responses without resort to explicit time delays. They also suggest a functional role for motion opponency in eliminating false motion signals.

Human Cerebrospinal Fluid Induces Neuronal Excitability Changes in Resected Human Neocortical and Hippocampal Brain Slices.

Human cerebrospinal fluid (hCSF) has proven advantageous over conventional medium for culturing both rodent and human brain tissue. In addition, increased activity and synchrony, closer to the dynamic states exclusively recorded in vivo, were reported in rodent slices and cell cultures switching from artificial cerebrospinal fluid (aCSF) to hCSF. This indicates that hCSF possesses properties that are not matched by the aCSF, which is generally used for most electrophysiological recordings. To evaluate the possible significance of using hCSF as an electrophysiological recording medium, also for human brain tissue, we compared the network and single-cell firing properties of human brain slice cultures during perfusion with hCSF and aCSF. For measuring the overall activity from a majority of neurons within neocortical and hippocampal human slices, we used a microelectrode array (MEA) recording technique with 252 electrodes covering an area of 3.2 × 3.2 mm2. A second CMOS-based MEA with 4225 sensors on a 2 × 2 mm2 area was used for detailed mapping of action potential waveforms and cell identification. We found that hCSF increased the number of active electrodes and neurons and the firing rate of the neurons in the slices and induced an increase in the numbers of single channel and population bursts. Interestingly, not only an increase in the overall activity in the slices was observed, but a reconfiguration of the network could also be detected with specific activation and inactivation of subpopulations of neuronal ensembles. In conclusion, hCSF is an important component to consider for future human brain slice studies, especially for experiments designed to mimic parts of physiology and disease observed in vivo.