Spread of pathological human Tau from neurons to oligodendrocytes and loss of high-firing pyramidal neurons in aging mice.

Intracellular aggregation of hyperphosphorylated Tau (pTau) in the brain is associated with cognitive and motor impairments, and ultimately neurodegeneration. We investigate how human pTau affects cells and network activity in the hippocampal formation of the THY-Tau22 tauopathy model mice in vivo. We find that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to neurodegeneration, and we establish that pTau spreads to oligodendrocytes.

In vivo electrophysiological study of the targeting of 5-HT receptor-expressing cortical interneurons by the multimodal antidepressant, vortioxetine.

The antidepressant vortioxetine has high affinity for the ionotropic 5-HT receptor (5-HT R) as well as other targets including the 5-HT transporter. The procognitive effects of vortioxetine have been linked to altered excitatory:inhibitory balance in cortex. Thus, vortioxetine purportedly inhibits cortical 5-HT R-expressing interneurons (5-HT R-INs) to disinhibit excitatory pyramidal neurons.

Phosphodiesterase 4 inhibition affects both the direct and indirect pathway: an electrophysiological study examining the tri-phasic response in the substantia nigra pars reticulata.

Fronto-striatal circuits constitute the neurobiological basis of many neuropsychiatric disorders. Part of the intracellular signaling within these circuits, including its dopaminergic modulation, is regulated by the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling cascade. Based on the overall expression in human fronto-striatal circuitry, we tested the effects of a cAMP selective phosphodiesterase 4 (PDE4) inhibitor on the tri-phasic response in the dorsomedial substantia nigra pars reticulata (SNr) upon stimulation of the infralimbic cortex in rats.

Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus.

Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine-induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the hippocampus.

Pharmacological Evidence for 5-HT6 Receptor Modulation of 5-HT Neuron Firing in Vivo.

5-Hydroxytryptamine (5-HT) neurons in the midbrain dorsal raphe nucleus (DRN) are implicated in the drug treatment and pathophysiology of a wide variety of neuropsychiatric disorders. Accumulating evidence suggests that 5-HT6 receptors may be located and functional in the DRN; therefore, 5-HT6 receptor ligands may have potential as novel modulators of 5-HT neurotransmission. The current study investigated the effect of intravenous (i.