Developmental trajectory of the endocannabinoid system in human dorsolateral prefrontal cortex

ABSTRACT: BACKGROUND: Endocannabinoids provide control over cortical neurotransmission. We investigated the developmental expression of key genes in the endocannabinoid system across human postnatal life and determined whether they correspond to the development of markers for inhibitory interneurons, which shape cortical development. We used microarray with qPCR validation and in situ hybridisation to quantify mRNA for the central endocannabinoid receptor CB1R, endocannabinoid synthetic enzymes (DAGLalpha for 2-arachidonylglycerol [2- AG] and NAPE-PLD for anandamide), and inactivating enzymes (MGL and ABHD6 for 2- AG and FAAH for anandamide) in human dorsolateral prefrontal cortex (39 days - 49 years). RESULTS: CB1R mRNA decreases until adulthood, particularly in layer II, after peaking between neonates and toddlers. DAGLalpha mRNA expression is lowest in early life and adulthood, peaking between school age and young adulthood. MGL expression declines after peaking in infancy, while ABHD6 increases from neonatal age. NAPE-PLD and FAAH expression increase steadily after infancy, peaking in adulthood. CONCLUSIONS: Stronger endocannabinoid regulation of presynaptic neurotransmission in both supragranular and infragranular cortical layers as indexed through higher CB1R mRNA may occur within the first few years of human life. After adolescence, higher mRNA levels of the anandamide synthetic and inactivating enzymes NAPE-PLD and FAAH suggest that a late developmental switch may occur where anandamide is more strongly regulated after adolescence than earlier in life. Thus, expression of key genes in the endocannabinoid system changes with maturation of cortical function.     

The laminar pattern of resting state in human cerebral cortex

Resting state functional Magnetic Resonance Imaging (RS-fMRI) provides the means to measure neuronal activity. One of the most commonly used methods to explore the RS-fMRI signal is the Probabilistic Independent Component Analysis (PICA). PICA allows to depict brain functional connectivity (FC) networks. Yet most of the IC maps obtained with this method do not represent any particular FC network. Consequently, those IC maps are classified as artifacts or noise of an unknown source. We hypothesized that the unexplained RS-fMRI signal patterns that are picked up by the PICA can be related to the differences in oxygen metabolism and blood flow in cortical layers. This study aimed at (1) providing preliminary evidence to the effects of laminar organization of neocortex on the RS-fMRI signal, and (2) evaluating the application of laminar maps to aid the classification of IC maps. We created laminar maps 1–4 that depict relative cortical thickness of layers IV and VI. Our data show that the RS-fMRI signal is significantly related to the relative thickness of the cortical layer VI but not layer IV. Importantly, the laminar maps 1–4 overlap with four separate IC maps. Thus, the laminar maps 1–4 improve classification and interpretation of the IC maps. Moreover, the laminar maps 1–4 may be considered as FC networks that are the bridging piece between particular cognitive functions. Together, these data provide preliminary evidence to the fundamental questions about the role of cortical layering in the RS-fMRI signal and brain FC networks.     

Study of the effects of EHF radiation on induced potentials in the cerebral cortex

Changes in the induced-potential components with direct EHF action on the cerebral cortex are shown in experiments with cats.Nizhny Novgorod Medical Institute. Translated from Izvestiya Vysshikh Uchebnykh Zavedenii, Radiofizika, Vol. 37, No. 1, pp. 138–144, January, 1994.     

Genomic responses in rat cerebral cortex after traumatic brain injury

Background  

Traumatic brain injury (TBI) initiates a complex sequence of destructive and neuroprotective cellular responses. The initial mechanical injury is followed by an extended time period of secondary brain damage. Due to the complicated pathological picture a better understanding of the molecular events occurring during this secondary phase of injury is needed. This study was aimed at analysing gene expression patterns following cerebral cortical contusion in rat using high throughput microarray technology with the goal of identifying genes involved in an early and in a more delayed phase of trauma, as genomic responses behind secondary mechanisms likely are time-dependent.     

Depth-resolved imaging of functional activation in the rat cerebral cortex using optical coherence tomography

Co-registered optical coherence tomography (OCT) and video microscopy of the rat somatosensory cortex were acquired simultaneously through a thinned skull during forepaw electrical stimulation. Fractional signal change measured by OCT revealed a functional signal time course corresponding to the hemodynamic signal measurement made with video microscopy. OCT can provide high-resolution, cross-sectional images of functional neurovascular activation and may offer a new tool for basic neuroscience research in the important rat cerebral cortex model.     

Chemosensory properties of murine nasal and cutaneous trigeminal neurons identified by viral tracing

Background  

Somatosensation of the mammalian head is mainly mediated by the trigeminal nerve that provides innervation of diverse tissues like the face skin, the conjunctiva of the eyes, blood vessels and the mucouse membranes of the oral and nasal cavities. Trigeminal perception encompasses thermosensation, touch, and pain. Trigeminal chemosensation from the nasal epithelia mainly evokes stinging, burning, or pungent sensations. In vitro characterization of trigeminal primary sensory neurons derives largely from analysis of complete neuronal populations prepared from sensory ganglia. Thus, functional properties of primary trigeminal afferents depending on the area of innervation remain largely unclear.     

Some features of sensing by cochlear neurons of low-frequency signals

Some features of sensing by human cochlear neurons of the infrasound vibrations generated by a change in frequency and volume of the audible range are discussed. It has been shown that auditory neurons respond to a volume envelope that selects corresponding infrasonic frequencies for their further processing. This mechanism is possible if the ear operates nonlinearly performing detection with further time averaging of no less than over 40–50 ms. If the frequency of the sound code coincides with any rhythm of the brain, resonance may occur, increasing the amplitude of the corresponding rhythm.     

Serum anticholinergic activity and cerebral cholinergic dysfunction: An EEG study in frail elderly with and without delirium

Background

Delirium increases morbidity, mortality and healthcare costs especially in the elderly. Serum anticholinergic activity (SAA) is a suggested biomarker for anticholinergic burden and delirium risk, but the association with cerebral cholinergic function remains unclear. To clarify this relationship, we prospectively assessed the correlation of SAA with quantitative electroencephalography (qEEG) power, delirium occurrence, functional and cognitive measures in a cross-sectional sample of acutely hospitalized elderly (> 80 y) with high dementia and delirium prevalence.

Methods

61 consecutively admitted patients over 80 years underwent an extensive clinical and neuropsychological evaluation. SAA was determined by using radio receptor assay as developed by Tune, and standard as well as quantitative EEGs were obtained.

Results

15 patients had dementia with additional delirium (DD) according to expert consensus using DSM-IV criteria, 31 suffered from dementia without delirium (D), 15 were cognitively unimpaired (CU). SAA was clearly detectable in all patients but one (mean 10.9 ± 7.1 pmol/ml), but was not associated with expert-panel approved delirium diagnosis or cognitive functions. Delirium-associated EEG abnormalities included occipital slowing, peak power and alpha decrease, delta and theta power increase and slow wave ratio increase during active delirious states. EEG measures correlated significantly with cognitive performance and delirium severity, but not with SAA levels.

Conclusion

In elderly with acute disease, EEG parameters reliable indicate delirium, but SAA does not seem to reflect cerebral cholinergic function as measured by EEG and is not related to delirium diagnosis.     

Synchrony between orientation-selective neurons is modulated during adaptation-induced plasticity in cat visual cortex

Background  

Visual neurons respond essentially to luminance variations occurring within their receptive fields. In primary visual cortex, each neuron is a filter for stimulus features such as orientation, motion direction and velocity, with the appropriate combination of features eliciting maximal firing rate. Temporal correlation of spike trains was proposed as a potential code for linking the neuronal responses evoked by various features of a same object. In the present study, synchrony strength was measured between cells following an adaptation protocol (prolonged exposure to a non-preferred stimulus) which induce plasticity of neurons' orientation preference.     

Co-release of noradrenaline and dopamine in the cerebral cortex elicited by single train and repeated train stimulation of the locus coeruleus

Background  

Previous studies by our group suggest that extracellular dopamine (DA) and noradrenaline (NA) may be co-released from noradrenergic nerve terminals in the cerebral cortex. We recently demonstrated that the concomitant release of DA and NA could be elicited in the cerebral cortex by electrical stimulation of the locus coeruleus (LC). This study analyses the effect of both single train and repeated electrical stimulation of LC on NA and DA release in the medial prefrontal cortex (mPFC), occipital cortex (Occ), and caudate nucleus. To rule out possible stressful effects of electrical stimulation, experiments were performed on chloral hydrate anaesthetised rats.     

Biosilicification (chalcedony) in human cerebral cortex, hippocampus and cerebellum from aged patients

Aluminum and silicon have been observed to be present in the human degenerated brain and normal elderly brains by using a combination of scanning electron microscopy and X-ray spectrometry (EDS-SEM). Al and Si of electric organs were also reported - in electrocytes and cholinergic nerves - from living electric fish (family Rajidae). A biogenically produced crystalline mineral phase (i.e., chalcedony) has also been observed in electric organs by using a mineralogical microscope. Based on this evidence we decided to explore the presence of chalcedony (SiO(2)) in the human central nervous system (CNS). Sections from aged patients (mean, 81 years) were collected after autopsy and observed using a Leica DMLP mineralogical microscope. Chalcedony was detected in cerebral cortex and cerebellum. In plane-polarized light, chalcedony is rounded in shape, 12-20mum in size, translucent, with a low refraction index. The crossed-polarizer image shows first order birefringence color (grey-white) and radial extinction. Chalcedony was also detected in the hippocampus in large amounts and sizes (50-60mum). Chalcedony is a microcrystalline fibrous form of silica. It consists of nanoscale intergrowths of quartz and the optically length-slow fibrous silica polymorph moganite. Chalcedony precipitation occurs at a specific pH (7-8) and oxidation potential (Eh; 0.0 to -0.2) in geological environments. This observation supports the important role played by pH and Eh conditions in silica precipitation in elderly brains, as has also been reported in peripheral cholinergic nerves in electric organ from living electric fish. Carbonic anhydrases (CAs) (silicase) are involved in physiological pH regulation and may also be participating in the polymerization-depolymerization of chalcedony in the human brain. This is the first time a biogenically produced crystalline mineral phase (i.e., chalcedony) has been observed in the human CNS from aged patients.     

Elevated intracellular chloride level in albino visual cortex neurons is mediated by Na-K-Cl co-transporter

Background  

During development the switch from a depolarizing to a hyperpolarizing action of GABA is a consequence of a decrease of the Na⁺-K⁺-2Cl^- co-transporter (NKCC1, Cl^--uptake) and increase of the K⁺-Cl^- co-transporter (KCC2, Cl^--extrusion) expression. However albino visual cortex neurons don't show a corresponding decrease in intracellular chloride concentration during development of the visual system as compared to pigmented animals.     

Operating principles of the cerebral cortex as a six-layered network in primates: beyond the classic canonical circuit model

The cerebral cortex performs its computations with many six-layered fundamental units, collectively spreading along the cortical sheet. What is the local network structure and the operating dynamics of such a fundamental unit? Previous investigations of primary sensory areas revealed a classic “canonical” circuit model, leading to an expectation of similar circuit organization and dynamics throughout the cortex. This review clarifies the different circuit dynamics at play in the higher association cortex of primates that implements computation for high-level cognition such as memory and attention. Instead of feedforward processing of response selectivity through Layers 4 to 2/3 that the classic canonical circuit stipulates, memory recall in primates occurs in Layer 5/6 with local backward projection to Layer 2/3, after which the retrieved information is sent back from Layer 6 to lower-level cortical areas for further retrieval of nested associations of target attributes. In this review, a novel “dynamic multimode module (D3M)” in the primate association cortex is proposed, as a new “canonical” circuit model performing this operation.     

A neurochemical map of the developing amphioxus nervous system

ABSTRACT: BACKGROUND: Amphioxus, representing the most basal group of living chordates, is the best available proxy for the last invertebrate ancestor of the chordates. Although the central nervous system (CNS) of amphioxus comprises only about 20,000 neurons (as compared to billions in vertebrates), the developmental genetics and neuroanatomy of amphioxus are strikingly vertebrate-like. In the present study, we mapped the distribution of amphioxus CNS cells producing distinctive neurochemicals. To this end, we cloned genes encoding biosynthetic enzymes and/or transporters of the most common neurotransmitters and assayed their developmental expression in the embryo and early larva. RESULTS: By single and double in situ hybridization experiments, we identified glutamatergic, GABAergic/glycinergic, serotonergic and cholinergic neurons in developing amphioxus. In addition to characterizing the distribution of excitatory and inhibitory neurons in the developing amphioxus CNS, we observed that cholinergic and GABAergic/glycinergic neurons are segmentally arranged in the hindbrain, whereas serotonergic, glutamatergic and dopaminergic neurons are restricted to specific regions of the cerebral vesicle and the hindbrain. We were further able to identify a discrete group of GABAergic and glutamatergic interneurons and cholinergic motoneurons at level of the primary motor center (PMC), the major integrative center of sensory and motor stimuli of the amphioxus nerve cord. CONCLUSIONS: In this study, we assessed neuronal differentiation in the developing amphioxus nervous system and compiled the first neurochemical map of the amphioxus CNS. This map is a first step towards a full characterization of the neurotransmitter signature of previously described nerve cell types in the amphioxus CNS, such as motoneurons and interneurons. The most striking discovery was that sub-populations of neurons become differentiated for producing distinctive neurochemicals well before the outgrowth of neurites establishes the definite neurocircuitry.     

Responses of neurons to click-pairs as simulated echoes: auditory nerve to auditory cortex

When two identical sounds are presented from different locations with a short interval between them, the perception is of a single sound source at the location of the leading sound. This "precedence effect" is an important behavioral phenomenon whose neural basis is being increasingly studied. For this report, neural responses were recorded to paired clicks with varying interstimulus intervals, from several structures of the ascending auditory system in unanesthetized animals. The structures tested were the auditory nerve, anteroventral cochlear nucleus, superior olivary complex, inferior colliculus, and primary auditory cortex. The main finding is a progressive increase in the duration of the suppressive effect of the leading sound (the conditioner) on the response to the lagging sound (the probe). The first major increase occurred between the lower brainstem and inferior colliculus, and the second between the inferior colliculus and auditory cortex. In neurons from the auditory nerve, cochlear nucleus, and superior olivary complex, 50% recovery of the response to the probe occurred, on average, for conditioner and probe intervals of approximately 2 ms. In the inferior colliculus, 50% recovery occurred at an average separation of approximately 7 ms, and in the auditory cortex at approximately 20 ms. Despite these increases in average recovery times, some neurons in every structure showed large responses to the probe within the time window for precedence (approximately 1-4 ms for clicks). This indicates that during the period of the precedence effect, some information about echoes is retained. At the other extreme, for some cortical neurons the conditioner suppressed the probe response for intervals of up to 300 ms. This is in accord with behavioral results that show dominance of the leading sound for an extended period beyond that of the precedence effect. Other transformations as information ascended included an increased variety in the shapes of the recovery functions in structures subsequent to the nerve, and neurons "tuned" to particular conditioner-probe intervals in the auditory cortex. These latter are reminiscent of neurons tuned to echo delay in bats, and may contribute to the perception of the size of the acoustic space.     

Dynamic changes in GABA<Subscript>A</Subscript>receptors on basal forebrain cholinergic neurons following sleep deprivation and recovery

Background  

The basal forebrain (BF) cholinergic neurons play an important role in cortical activation and arousal and are active in association with cortical activation of waking and inactive in association with cortical slow wave activity of sleep. In view of findings that GABA_A receptors (Rs) and inhibitory transmission undergo dynamic changes as a function of prior activity, we investigated whether the GABA_ARs on cholinergic cells might undergo such changes as a function of their prior activity during waking vs. sleep.     

Treatment of trigeminal ganglion neurons in vitro with NGF,GDNF or BDNF: effects on neuronal survival,neurochemical properties and TRPV1-mediated neuropeptide secretion

Background  

Nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) all play important roles in the development of the peripheral sensory nervous system. Additionally, these growth factors are proposed to modulate the properties of the sensory system in the adult under pathological conditions brought about by nerve injury or inflammation. We have examined the effects of NGF, GDNF and BDNF on adult rat trigeminal ganglion (TG) neurons in culture to gain a better understanding of how these growth factors alter the cytochemical and functional phenotype of these neurons, with special attention to properties associated with nociception.     

Optical coherence Doppler tomography quantifies laser speckle contrast imaging for blood flow imaging in the rat cerebral cortex

A dual-imaging modality is demonstrated for high-resolution quantitative imaging of local cerebral blood flow in the rat cortex by combining simultaneous spectral-domain Doppler optical coherence tomography (SDOCT) and full-field laser speckle contrast imaging (LSCI). Preliminary studies in tissue flow phantom and cocaine-induced cerebral blood flow changes indicated that by correlating coregistered cortical arterial blood flow, the relative measurement of flow changes by LSCI could be accurately calibrated by the absolute flow imaging provided by SDOCT (least square fit, r(2) approximately 0.96). Quantitative LSCI of cerebral blood flow is crucial to the quantitative analyses of the spatiotemporal hemodynamics of functional brain activations and thus improved understanding of neural process.