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Neuropeptides are commonly colocalized with classical neurotransmitters, yet there is little evidence for peptidergic neurotransmission in the mammalian CNS. We performed whole-cell patch-clamp recording from rodent thalamic brain slices and repetitively stimulated corticothalamic fibers to strongly activate NPY-containing GABAergic reticular thalamic (RT) neurons. This resulted in long-lasting: (∼10 sec) feedforward slow IPSPs (sIPSPs) in RT cells, which were mimicked and blocked by NPY[sub1] (Y[sub1]) receptor agonists and antagonists, respectively, and were present in wild-type mice but absent in NPY[sup-/-] mice. NPYergic sIPSPs were mediated via G-proteins and G-protein-activated, inwardly rectifying potassium channels, as evidenced by sensitivity to GDP-β-S and 0.1 mM Ba&sup2+;. In rat RT neurons, NPYergic sIPSPs were also present but were surprisingly absent in the major synaptic targets of RT, thalamic relay neurons, where instead robust GABA[subB] IPSPs occurred. In vitro oscillatory network responses in rat thalamus were suppressed and augmented by Y[sub1] agonists and antagonists, respectively. These findings provide evidence for segregation of postsynaptic actions between two targets of RT cells and support a role for endogenously released NPY within RT in the regulation of oscillatory thalamic responses relevant to sleep and epilepsy. [ABSTRACT FROM AUTHOR]

Focuses on a study which examined dynamic Gamma-aminobutyric acid[subA] receptor subtype-specific modulation of the synchrony and duration of thalamic oscillations. Role of intra-thalamic reticular nucleus inhibition; Differences between the effects of clonazepam in rats and mice; Implications for anti-absence drug design.

Provides information on a study that tested the effects of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide on thalamocortical neurons using whole-cell patch-clamp techniques applied to visualized neurons in rat brain slices. Methodology of the study; Results and discussion on the study.

Neuropeptide Y (NPY) is widely expressed throughout the nervous system and is known to reduce excitatory (but also inhibitory) synaptic transmission in many CNS areas, leading to the proposal that it is an endogenous antiepileptic agent, in the neocortex, where NPY is present in γ-aminobutyric acid (GABA)ergic interneurons, its effects on inhibitory and excitatory synaptic activities have not been completely explored. Here we report that NPY application elicits a long-lasting decrease in evoked excitatory postsynaptic current amplitude and a delayed, long-lasting into crease in the amplitude of evoked monosynaptic inhibitory postsynaptic current (IPSC) in layer V pyramidal neurons of rat neocortex. The novel, late, NPY-mediated increase of inhibitory synaptic transmission is caused by modulation of Ca[sup 2+]-dependent GABA release onto pyramidal neurons, as it was accompanied by an increase in Ca[sup 2+]-dependent miniature IPSC frequency. NPY decreased evoked monosynaptic IPSCs in GABAergic interneurons, indicating that this neuropeptide has differential effects on different neuronal subtypes in the neocortex. Each of these NPY actions would decrease excitability in cortical circuits, a result that has important implications for both physiological neocortical operations as well as pathophysiological epileptiform activities. [ABSTRACT FROM AUTHOR]

The article discusses the study on the role of receptor tyrosine kinase ErbB4 in the regulation of the sensitivity of the thalamic reticular nucleus (TRN) to cortical inputs. It details how the study was conducted which involved a hypothetical model wherein thalamic ErbB4 function was integrated across synapses. The results reportedly revealed that the loss of ErbB4 in somatostatin inhibitory neurons of the TRN improves top-down cortical feedback.

For the human brain to operate, populations of neurons across anatomical structures must coordinate their activity within milliseconds. To date, our understanding of such interactions has remained limited. We recorded directly from the hippocampus (HPC), posteromedial cortex (PMC), ventromedial/orbital prefrontal cortex (OFC), and the anterior nuclei of the thalamus (ANT) during two experiments of autobiographical memory processing that are known from decades of neuroimaging work to coactivate these regions. In 31 patients implanted with intracranial electrodes, we found that the presentation of memory retrieval cues elicited a significant increase of low frequency (LF < 6 Hz) activity followed by cross-regional phase coherence of this LF activity before select populations of neurons within each of the four regions increased high-frequency (HF > 70 Hz) activity. The power of HF activity was modulated by memory content, and its onset followed a specific temporal order of ANT→HPC/PMC→OFC. Further, we probed cross-regional causal effective interactions with repeated electrical pulses and found that HPC stimulations cause the greatest increase in LF-phase coherence across all regions, whereas the stimulation of any region caused the greatest LF-phase coherence between that particular region and ANT. These observations support the role of the ANT in gating, and the HPC in synchronizing, the activity of cortical midline structures when humans retrieve self-relevant memories of their past. Our findings offer a fresh perspective, with high temporal fidelity, about the dynamic signaling and underlying causal connections among distant regions when the brain is actively involved in retrieving self-referential memories from the past. [ABSTRACT FROM AUTHOR]

Presents the results of a study which was conducted to test the range of inhibitory influences of single reticular nucleus (nRT) neurons upon relay neurons. Results indicating that there is a heterogeneity of inhibitory interactions between nRt and ventrobasal thalamocortical (VB) cells.

Determines the threshold and minimal delay of gamma-aminobutyric acid (GABA)-mediated rebound burst firing in nRt cells compared with relay neurons. Demonstration of the potential role of GABA synapse in synchronizing thalamic network activity; Characteristics of rebound bursts in thalamic cells; Slow inhibitory postsynaptic potential-mediated burst firing.

Reports on how chortical cholinergic activation may reduce some forms of intralaminar inhibition, promote intracolumnar inhibition, and change the direction of information flow within cortical circuits. Role of cholinergic systems within the brain; Methods used in testing cholinergic switching within the brain.

Persistent sodium channel activity modulates neuronal gain in a neurotransmitter-dependent fashion. Previous studies have suggested that persistent and spike-related sodium channel activities are mediated by separate species. In this issue of Neuron, show that a single channel population is sufficient to explain both gating behaviors. A simple allosteric model is provided that can explain the results. [Copyright &y& Elsevier]

The authors discuss the reemergence of the role of cable properties in the initiation of action potential. They state two distinct paths of the cable theory, such as longitudinal way along central conductor and transversely through membrane or cable sheating. They add that either lower passive load or greater sodium ions (Na+) influx will favor local initiation or increase depolarization according to cable theory.

The article discusses the role of neurons in controlling sleep-to-wake transition and highlights the role of peptides called Hypocretins (Herts) which is secreted by hypothalamic neurons known to promote wakefulness. It reports that the study provides functional evidence that locus coeruleus (LC) is the main downstream effector which mediates the effects of Hcrt to promote wakefulness during nonrapid eye movement (NREM) during the inactive period.

Chen Y, Lu J, Pan H, Zhang Y, Wu H, Xu K, Liu X, Jiang Y, Bao X, Yao Z, Ding K, Lo WH, Qiang B, Chan P, Shen Y, Wu X Ann Neurol 2003;54:239–243 Direct sequencing of exons 3 to 35 and the exon–intron boundaries of the CACNA1H gene was conducted in 118 childhood absence epilepsy patients of Han ethnicity recruited from North China. Sixty-eight variations have been detected in the CACNA1H gene, and among the variations identified, 12 were missense mutations and found only in 14 of the 118 patients in a heterozygous state, but not in any of 230 unrelated controls. The identified missense mutations occurred in the highly conserved residues of the T-type calcium channel gene. Our results suggest that CACNA1H might be an important susceptibility gene involved in the pathogenesis of childhood absence epilepsy. [ABSTRACT FROM AUTHOR]

Focuses on evidence that shows reliability of propagation for neocortical pyramidal neurons. Signs of electrical activity in individual submicron branch points and axonal swellings; Characterization of neurons in the central nervous system by complex axonal arborization patterns.

The article offers information on complementary metal-oxide semiconductor (CMOS) based highly scalable flexible neural electrode interface. It discusses that the existing electrophysiological devices are limited by their scalability in capturing this cortex-wide activity, it also discusses about Flex2Chip that interconnects using microfabricated electrode pads suspended by thin support arms and discussed limitation of CMOS.

GABAergic neurons of the thalamic reticular nucleus (nRt) provide thalamocortical relay neurons with feedback inhibition that influences sensory processing and thalamocortical rhythm generation. Mutual interactions between reticular neurons coordinate oscillatory activities developed within the network during normal sleep and in absence epilepsy, but the chemical versus electrical nature of these connections and their functional influence remain controversial. Here, we investigated the incidence and spatial extent of intra-nRt connectivity in vitro in horizontal and coronal thalamic slices from rat. Laser scanning photostimulation activated presynaptic nRt cells during patch-clamp recordings of postsynaptic neurons. Photolysis of caged glutamate evoked GABAergic IPSCs and/or depolarizing events (spikelets, mediated via electrical coupling) in a large proportion of neurons, thus indicating connectivity with presynaptic cell(s). Synaptic inputs were organized along the major axis of the nucleus in the same orientation as, but commonly exceeding the extent of, dendritic arborization of the postsynaptic neuron. In the anteroposterior (horizontal) plane, chemical connectivity had higher incidence (60% of recorded neurons vs 40% in vertical plane) and longer spatial extent, whereas in the dorsoventral (vertical) plane, electrical coupling dominated (47% incidence vs 37% in horizontal plane) and was more widely distributed. These data demonstrate that both electrical and chemical synapses are prominent within nRt and suggest different roles for the two types of connections. We thus propose that, along the vertical plane, electrical connectivity will promote coordinated rhythmic activity of sleep and/or thalamocortical epilepsy, whereas along the horizontal plane, chemical connectivity will oppose widespread thalamocortical synchronization and modulate sensory throughput. [ABSTRACT FROM AUTHOR]

Valproate (VPA) can suppress absence and other seizures, but its precise mechanisms of action are not completely understood. We investigated whether VPA influences the expression of neuropeptide Y (NPY), an endogenous anticonvulsant. Chronic VPA administration to young rats (300-600 mg ⋅ kg-1 ⋅ d-1 in divided doses over 4 d) resulted in a 30-50% increase in NPY mRNA and protein expression in the nucleus reticularis thalami (nRt) and hippocampus, but not in the neocortex, as shown by real-time PCR, radioimmunoassay, and immunohistochemistry. No increased expression was observed after a single acute dose of VPA. Chronic treatment with the pharmacologically inactive VPA analog octanoic acid did not elicit changes in NPY expression. No significant expression changes could be shown for the mRNAs of the Y1 receptor or of the neuropeptides somatostatin, vasoactive intestinal polypeptide, and choleocystokinin. Fewer synchronous spontaneous epileptiform oscillations were recorded in thalamic slices from VPA-treated animals, and oscillation duration as well as the period of spontaneous and evoked oscillations were decreased. Application of the Y1 receptor inhibitor N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-amide (BIBP3226) enhanced thalamic oscillations, indicating that NPY is released during those oscillations and acts to downregulate oscillatory strength. Chronic VPA treatment significantly potentiated the effect of BIBP3226 on oscillation duration but not on oscillation period. These results demonstrate a novel mechanism for the antiepileptic actions of chronic VPA therapy. [ABSTRACT FROM AUTHOR]

Hyperexcitability of brain circuits is a common feature of autism spectrum disorders (ASDs). Genetic deletion of a chromatin-binding protein, retinoic acid induced 1 (RAI1), causes Smith-Magenis syndrome (SMS). SMS is a syndromic ASD associated with intellectual disability, autistic features, maladaptive behaviors, overt seizures, and abnormal electroencephalogram (EEG) patterns. The molecular and neural mechanisms underlying abnormal brain activity in SMS remain unclear. Here we show that panneural Rai1 deletions in mice result in increased seizure susceptibility and prolonged hippocampal seizure duration in vivo and increased dentate gyrus population spikes ex vivo. Brain-wide mapping of neuronal activity pinpointed selective cell types within the limbic system, including the hippocampal dentate gyrus granule cells (dGCs) that are hyperactivated by chemoconvulsant administration or sensory experience in Rai1-deficient brains. Deletion of Rai1 from glutamatergic neurons, but not from gamma-aminobutyric acidergic (GABAergic) neurons, was responsible for increased seizure susceptibility. Deleting Rai1 from the Emx1Cre-lineage glutamatergic neurons resulted in abnormal dGC properties, including increased excitatory synaptic transmission and increased intrinsic excitability. Our work uncovers the mechanism of neuronal hyperexcitability in SMS by identifying Rai1 as a negative regulator of dGC intrinsic and synaptic excitability. [ABSTRACT FROM AUTHOR]