It Takes T to Tango

AbstractOf three recently cloned T-type voltage-gated calcium channels, α1g is most likely responsible for burst firing in thalamic relay cells. These neurons burst during various thalamocortical oscillations including absence seizures. In this issue of Neuron, Kim et al. inactivated α1g, and resultant mice were deficient in relay cell bursting and resistant to GABAB receptor-dependent absence seizures, suggesting roles for α1g and relay cell bursting in absences

Coordinated neuronal ensembles in primary auditory cortical columns.

The synchronous activity of groups of neurons is increasingly thought to be important in cortical information processing and transmission. However, most studies of processing in the primary auditory cortex (AI) have viewed neurons as independent filters; little is known about how coordinated AI neuronal activity is expressed throughout cortical columns and how it might enhance the processing of auditory information. To address this, we recorded from populations of neurons in AI cortical columns of anesthetized rats and, using dimensionality reduction techniques, identified multiple coordinated neuronal ensembles (cNEs), which are groups of neurons with reliable synchronous activity. We show that cNEs reflect local network configurations with enhanced information encoding properties that cannot be accounted for by stimulus-driven synchronization alone. Furthermore, similar cNEs were identified in both spontaneous and evoked activity, indicating that columnar cNEs are stable functional constructs that may represent principal units of information processing in AI

LETTERS Parvalbumin neurons and gamma rhythms enhance cortical circuit performance

Synchronized oscillations and inhibitory interneurons have important and interconnected roles within cortical microcircuits. In particular, interneurons defined by the fast-spiking phenotype and expression of the calcium-binding protein parvalbumin We first developed a versatile system to selectively express microbial opsins, enhanced Natronomonas pharaonis halorhodopsin (eNpHR) or channelrhodopsin-2 (ChR2), in fast-spiking parvalbumin (PV) interneurons. Although opsin expression can be targeted with a PV promoter fragment 15 , the resulting level of expression was insufficient to drive action potentials reliably (data not shown). We therefore devised (Supplementary Information) a Cre-recombinasedependent adeno-associated virus (AAV) expression system carrying a reversed Cre-dependent eNpHR-eYFP (enhanced yellow fluorescent protein) or ChR2-eYFP AAV5 vectors were stereotactically injected into the cortex of PV::Cre transgenic mice. Numerous interneurons with eYFP fluorescence were observed We used this system to test whether PV interneuron activity could be involved in gamma oscillation generation in vivo. We injected Camk2a (CaMKIIa)::ChR2-eYFP and Cre-dependent eNpHR-eYFP AAV5 into the prefrontal cortex of PV::Cre transgenic mice, yielding simultaneous ChR2 expression in pyramidal (PY) neurons and eNpHR expression in fast-spiking PV interneurons Because inhibition of PV interneurons was found to suppress gamma power, we next sought to determine whether stimulating PV cells could elicit gamma oscillations in downstream PY neurons. To achieve precise and specific control of inputs to PV and PY neurons, we used brain slices from PV::Cre mice injected with Credependent ChR2-eYFP AAV5 in prefrontal cortex. Blue light drove spikes in PV interneurons and inhibited spikes in PY cells, as expecte

Author Correction: The CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms.

The originally published version of this Article contained errors in Figure 5, for which we apologise. In panel c, the scatter graph was inadvertently replaced with a scatter graph comprising a subset of data points from panel d. Furthermore, the legends to Figures 5c and 5d were inverted. These errors have now been corrected in both the PDF and HTML versions of the Article, and the incorrect version of Fig. 5c is presented in the Author Correction associated with this Article

The CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms.

CaMKII is one of the most studied synaptic proteins, but many critical issues regarding its role in synaptic function remain unresolved. Using a CRISPR-based system to delete CaMKII and replace it with mutated forms in single neurons, we have rigorously addressed its various synaptic roles. In brief, basal AMPAR and NMDAR synaptic transmission both require CaMKIIα, but not CaMKIIβ, indicating that, even in the adult, synaptic transmission is determined by the ongoing action of CaMKIIα. While AMPAR transmission requires kinase activity, NMDAR transmission does not, implying a scaffolding role for the CaMKII protein instead. LTP is abolished in the absence of CaMKIIα and/or CaMKIIβ and with an autophosphorylation impaired CaMKIIα (T286A). With the exception of NMDAR synaptic currents, all aspects of CaMKIIα signaling examined require binding to the NMDAR, emphasizing the essential role of this receptor as a master synaptic signaling hub

A mouse model of autism implicates endosome pH in the regulation of presynaptic calcium entry.

Psychoactive compounds such as chloroquine and amphetamine act by dissipating the pH gradient across intracellular membranes, but the physiological mechanisms that normally regulate organelle pH remain poorly understood. Interestingly, recent human genetic studies have implicated the endosomal Na+/H+ exchanger NHE9 in both autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). Plasma membrane NHEs regulate cytosolic pH, but the role of intracellular isoforms has remained unclear. We now find that inactivation of NHE9 in mice reproduces behavioral features of ASD including impaired social interaction, repetitive behaviors, and altered sensory processing. Physiological characterization reveals hyperacidic endosomes, a cell-autonomous defect in glutamate receptor expression and impaired neurotransmitter release due to a defect in presynaptic Ca2+ entry. Acute inhibition of synaptic vesicle acidification rescues release but without affecting the primary defect due to loss of NHE9

How Close Are We to Understanding What (if Anything) γ Oscillations Do in Cortical Circuits?

γ oscillations, which can be identified by rhythmic electrical signals ∼30-100 Hz, consist of interactions between excitatory and inhibitory neurons that result in rhythmic inhibition capable of entraining firing within local cortical circuits. Many possible mechanisms have been described through which γ oscillations could act on cortical circuits to modulate their responses to input, alter their patterns of activity, and/or enhance the efficacy of their outputs onto downstream targets. Recently, several studies have observed changes in behavior after optogenetically manipulating neocortical γ oscillations. Now, future studies should determine whether these manipulations elicit physiological correlates associated with specific mechanisms through which γ oscillations are hypothesized to modulate cortical circuit function. There are numerous such mechanisms, so identifying which ones are actually engaged by optogenetic manipulations known to affect behavior would help flesh out exactly how γ oscillations contribute to cortical circuit function under normal and/or pathological conditions