Diverse roles for the posteromedial thalamus in sensory-evoked cortical plasticity.

The posteromedial thalamus (POm) has extensive recurrent connectivity with the whisker-related primary somatosensory cortex (wS1) of rodents. However, its functional contribution to somatosensory processing in wS1 remains unclear. This article reviews several recent findings, which begin to elucidate the role of POm in sensory-evoked plasticity and discusses their implications for somatosensory processing.

Neuroprotective actions of leptin facilitated through balancing mitochondrial morphology and improving mitochondrial function.

Mitochondrial dysfunction has a recognised role in the progression of Alzheimer's disease (AD) pathophysiology. Cerebral perfusion becomes increasingly inefficient throughout ageing, leading to unbalanced mitochondrial dynamics. This effect is exaggerated by amyloid ß (Aß) and phosphorylated tau, two hallmark proteins of AD pathology. A neuroprotective role for the adipose-derived hormone, leptin, has been demonstrated in neuronal cells. However, its effects with relation to mitochondrial function in AD remain largely unknown. To address this question, we have used both a glucose-serum-deprived (CGSD) model of ischaemic stroke in SH-SY5Y cells and a Aß1-42 -treatment model of AD in differentiated hippocampal cells. Using a combination of 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and MitoRed staining techniques, we show that leptin prevents depolarisation of the mitochondrial membrane and excessive mitochondrial fragmentation induced by both CGSD and Aß1-42 . Thereafter, we used ELISAs and a number of activity assays to reveal the biochemical underpinnings of these processes. Specifically, leptin was seen to inhibit up-regulation of the mitochondrial fission protein Fis1 and down-regulation of the mitochondrial fusion protein, Mfn2. Furthermore, leptin was seen to up-regulate the expression and activity of the antioxidant enzyme, monoamine oxidase B. Herein we provide the first demonstration that leptin is sufficient to protect against aberrant mitochondrial dynamics and resulting loss of function induced by both CGSD and Aß1-42 . We conclude that the established neuroprotective actions of leptin may be facilitated through regulation of mitochondrial dynamics.

Development and validation of a cryogenic far-infrared diffraction grating spectrometer used to post-disperse the output from a Fourier transform spectrometer.

Recent advances in far-infrared detector technology have led to increases in raw sensitivity of more than an order of magnitude over previous state-of-the-art detectors. With such sensitivity, photon noise becomes the dominant noise component, even when using cryogenically cooled optics, unless a method of restricting the spectral bandpass is employed. The leading instrument concept features reflecting diffraction gratings, which post-disperse the light that has been modulated by a polarizing Fourier transform spectrometer (FTS) onto a detector array, thereby reducing the photon noise on each detector. This paper discusses the development of a cryogenic (4 K) diffraction grating spectrometer that operates over the wavelength range of 285 to 500 µm and was used to post-disperse the output from a room-temperature polarizing FTS. Measurements of the grating spectral response and diffraction efficiency are presented as a function of both wavelength and polarization to characterize the instrumental performance.

Higher-order thalamocortical circuits are specified by embryonic cortical progenitor types in the mouse brain.

The sensory cortex receives synaptic inputs from both first-order and higher-order thalamic nuclei. First-order inputs relay simple stimulus properties from the periphery, whereas higher-order inputs relay more complex response properties, provide contextual feedback, and modulate plasticity. Here, we reveal that a cortical neuron's higher-order input is determined by the type of progenitor from which it is derived during embryonic development. Within layer 4 (L4) of the mouse primary somatosensory cortex, neurons derived from intermediate progenitors receive stronger higher-order thalamic input and exhibit greater higher-order sensory responses. These effects result from differences in dendritic morphology and levels of the transcription factor Lhx2, which are specified by the L4 neuron's progenitor type. When this mechanism is disrupted, cortical circuits exhibit altered higher-order responses and sensory-evoked plasticity. Therefore, by following distinct trajectories, progenitor types generate diversity in thalamocortical circuitry and may provide a general mechanism for differentially routing information through the cortex.

Embryonic progenitor pools generate diversity in fine-scale excitatory cortical subnetworks.

The mammalian neocortex is characterized by a variety of neuronal cell types and precise arrangements of synaptic connections, but the processes that generate this diversity are poorly understood. Here we examine how a pool of embryonic progenitor cells consisting of apical intermediate progenitors (aIPs) contribute to diversity within the upper layers of mouse cortex. In utero labeling combined with single-cell RNA-sequencing reveals that aIPs can generate transcriptionally defined glutamatergic cell types, when compared to neighboring neurons born from other embryonic progenitor pools. Whilst sharing layer-associated morphological and functional properties, simultaneous patch clamp recordings and optogenetic studies reveal that aIP-derived neurons exhibit systematic biases in both their intralaminar monosynaptic connectivity and the post-synaptic partners that they target within deeper layers of cortex. Multiple cortical progenitor pools therefore represent an important factor in establishing diversity amongst local and long-range fine-scale glutamatergic connectivity, which generates subnetworks for routing excitatory synaptic information.