Phenethylamine is a substrate of monoamine oxidase B in the paraventricular thalamic nucleus

Monoamine oxidase (MAO) is a key enzyme responsible for the degradation of neurotransmitters and trace amines. MAO has two subtypes (MAO-A and MAO-B) that are encoded by different genes. In the brain, MAO-B is highly expressed in the paraventricular thalamic nucleus (PVT); however, its substrate in PVT remains unclear. To identify the MAO-B substrate in PVT, we generated Maob knockout (KO) mice and measured five candidate substrates (i.e., noradrenaline, dopamine, 3-methoxytyramine, serotonin, and phenethylamine [PEA]) by liquid chromatography tandem mass spectrometry. We showed that only PEA levels were markedly elevated in the PVT of Maob KO mice. To exclude the influence of peripheral MAO-B deficiency, we developed brain-specific Maob KO mice, finding that PEA in the PVT was increased in brain-specific Maob KO mice, whereas the extent of PEA increase was less than that in global Maob KO mice. Given that plasma PEA levels were elevated in global KO mice, but not in brain–specific KO mice, and that PEA passes across the blood–brain barrier, the substantial accumulation of PEA in the PVT of Maob KO mice was likely due to the increase in plasma PEA. These data suggest that PEA is a substrate of MAO-B in the PVT as well as other tissues.

INFLUENCE OF RAT CENTRAL THALAMIC NEURONS ON FORAGING BEHAVIOR IN A HAZARDOUS ENVIRONMENT

The basolateral amygdala (BL) is a major regulator of foraging behavior. Following BL inactivation, rats become indifferent to predators. However, at odds with the view that the amygdala detects threats and generate defensive behaviors, most BL neurons have reduced firing rates during foraging and at proximity of the predator. In search of the signals determining this unexpected activity pattern, this study considered the contribution of the central medial thalamic nucleus (CMT), which sends a strong projection to BL, mostly targeting its principal neurons. Inactivation of CMT or BL with muscimol abolished the rats’ normally cautious behavior in the foraging task. Moreover, unit recordings revealed that CMT neurons showed large but heterogeneous activity changes during the foraging task, with many neurons decreasing or increasing their discharge rates, with a modest bias for the latter. A generalized linear model revealed that CMT neurons encode many of the same task variables as principal BL cells. However, the nature (inhibitory vs. excitatory) and relative magnitude of the activity modulations seen in CMT neurons differed markedly from those of principal BL cells but were very similar to those of fast-spiking BL interneurons. Together, these findings suggest that, during the foraging task, CMT inputs fire some principal BL neurons, recruiting feedback interneurons in BL, resulting in the widespread inhibition of principal BL cells.

Cross-Streams Through the Ventral Posteromedial Thalamic Nucleus to Convey Vibrissal Information

Whisker detection is crucial to adapt to the environment for some animals, but how the nervous system processes and integrates whisker information is still an open question. It is well-known that two main parallel pathways through Ventral posteromedial thalamic nucleus (VPM) ascend to the barrel cortex, and classical theory suggests that the cross-talk from trigeminal nucleus interpolaris (Sp5i) to principal nucleus (Pr5) between the main parallel pathways contributes to the multi-whisker integration in barrel columns. Moreover, some studies suggest there are other cross-streams between the parallel pathways. To confirm their existence, in this study we used a dual-viral labeling strategy and high-resolution, large-volume light imaging to get the complete morphology of individual VPM neurons and trace their projections. We found some new thalamocortical projections from the ventral lateral part of VPM (VPMvl) to barrel columns. In addition, the retrograde-viral labeling and imaging results showed there were the large trigeminothalamic projections from Sp5i to the dorsomedial section of VPM (VPMdm). Our results reveal new cross-streams between the parallel pathways through VPM, which may involve the execution of multi-whisker integration in barrel columns.

Hippocampal CA1 pyramidal cells do not receive monosynaptic input from thalamic nucleus reuniens

Midline thalamic nuclei play a critical role in cognitive functions such as memory, decision-making and spatial navigation, by facilitating communication between the many brain regions involved in these processes. One canonical feature of thalamic interactions with the cortex or hippocampus appears to be that the thalamus receives input from, and projects to, excitatory neurons. Thalamic nucleus reuniens (NRe) is located on the midline and is viewed primarily as a relay from prefrontal cortex to hippocampal and entorhinal areas, although these connections are poorly defined at the cellular and synaptic level. Using electrophysiology and monosynaptic circuit-tracing, we found that pyramidal cells in CA1 receive no direct input from NRe. This contrasts starkly with prefrontal cortex, subiculum and entorhinal cortex, and indicates that NRe inputs to CA1 primarily drive local inhibition and not excitation they do in the other regions. The NRe to CA1 projection is thus a unique thalamic projection and as such is raising important questions about the function of NRe-mediated prefrontal control of the hippocampus.

Longitudinal thalamic white and grey matter changes associated with visual hallucinations in Parkinson’s disease

ObjectiveVisual hallucinations are common in Parkinson’s disease (PD) and associated with worse outcomes. Large-scale network imbalance is seen in PD-associated hallucinations, but mechanisms remain unclear. As the thalamus is critical in controlling cortical networks, structural thalamic changes could underlie network dysfunction in PD hallucinations.MethodsWe used whole-brain fixel-based analysis and cortical thickness measures to examine longitudinal white and grey matter changes in 76 patients with PD (15 hallucinators, 61 non-hallucinators) and 26 controls at baseline, and after 18 months. We compared white matter and cortical thickness, adjusting for age, gender, time-between-scans and intracranial volume. To assess thalamic changes, we extracted volumes for 50 thalamic subnuclei (25 each hemisphere) and mean fibre cross-section (FC) for white matter tracts originating in each subnucleus and examined longitudinal change in PD-hallucinators versus non-hallucinators.ResultsPD hallucinators showed white matter changes within the corpus callosum at baseline and extensive posterior tract involvement over time. Less extensive cortical thickness changes were only seen after follow-up. White matter connections from the right medial mediodorsal magnocellular thalamic nucleus showed reduced FC in PD hallucinators at baseline followed by volume reductions longitudinally. After follow-up, almost all thalamic subnuclei showed tract losses in PD hallucinators compared with non-hallucinators.InterpretationPD hallucinators show white matter loss particularly in posterior connections and in thalamic nuclei, over time with relatively preserved cortical thickness. The right medial mediodorsal thalamic nucleus shows both connectivity and volume loss in PD hallucinations. Our findings provide mechanistic insights into the drivers of network imbalance in PD hallucinations and potential therapeutic targets.

Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)-mediated plasticity in the paraventricular thalamic nucleus promotes a fundamental adaptation to stress

BACKGROUND: Habituation is defined as a progressive decline in response to repeated exposure to a familiar and predictable stimulus and is highly conserved across species. Disrupted habituation is a signature of post-traumatic stress disorder (PTSD). In rodents, habituation is observed in neural, neuroendocrine and behavioral responses to repeated exposure to the predictable and moderately intense stress or restraint. We previously demonstrated that lesions to the posterior division of the paraventricular thalamic nucleus (pPVT) impairs habituation. However, the underlying molecular mechanisms and specific neural connections among the pPVT and other brain regions that underlie habituation are unknown. METHODS: Behavioral and neuroendocrine habituation was assessed in adult male Sprague-Dawley restraints using the repeated restraint paradigm. Pan neuronal and Cre-dependent Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were used to chemogenetically inhibit the pPVT and the subpopulation of pPVT neurons that project to the medial prefrontal cortex (mPFC), respectively. Activity-regulated cytoskeleton-associated protein (Arc) expression was knocked down in the pPVT using siRNA directed towards Arc. Golgi staining was used to assess structural plasticity of pPVT neurons. Local field potential recordings were used to assess coherent neural activity between the pPVT and mPFC. The attentional set-shifting task was used to assess mPFC-dependent behavior. RESULTS: Here, we show that Arc promotes habituation by increasing stress-induced spinogenesis in the pPVT, increasing coherent neural activity with the mPFC, and improving mPFC-mediated cognitive flexibility. CONCLUSION: Our results demonstrate that Arc induction in the pPVT regulates habituation to repeated restraint and mPFC function.