Biology subjects

Tetzlaff, M. R.

Publications and source records attributed to Tetzlaff, M. R..

4 recordsLinked to original sources

bioRxiv2026

Peptide signaling in the paraventricular thalamus contributes to disrupted adult reward behaviors after early-life adversity

Early-life adversity (ELA) is strongly linked to emotional disorders characterized by dysregulated reward behaviors including diminished motivation for and enjoyment of rewards (anhedonia). However, how transient ELA leads to enduring disruptions of reward behaviors remains unclear. Using activity-dependent genetic labeling during ELA, we previously found that the paraventricular thalamic nucleus (PVT) uniquely distinguishes ELA from typical rearing, and inhibiting ELA-activated PVT cells in adult ELA mice rescued reward behaviors in a sex-specific manner. However, the cellular mechanisms by which ELA alters the function of PVT neurons enduringly, to impact adult reward behaviors is unresolved. Here, we probed potential gene expression mechanisms by assessing reward-induced gene translation selectively in early-life activated (TRAPed) PVT cells, and identified genes regulated by reward in a sex-specific way. Combining data- and hypothesis-driven approaches, we targeted the corticotropin-releasing hormone receptor type 1 (CRHR1) as potentially mediating ELA-induced disruptions of reward behaviors. We find that CRISPR-Cas9-mediated Crhr1 deletion in TRAPed-PVT cells restores typical reward behaviors in ELA mice. Our results provide insight into the developmental origin of mental illness and identify potentially powerful molecular targets for prevention or mitigation of the consequences of ELA on reward behaviors germane to human mental illness.

neuroscience↗

bioRxiv2025

A combined neuroanatomy, ex vivo imaging and immunohistochemistry defined MRI mask for the human paraventricular nucleus of the thalamus

The paraventricular nucleus of the thalamus (PVT) is an evolutionarily conserved midline thalamic structure known to contribute to arousal, interoceptive states, and motivated behaviors. Yet, a consensus anatomical definition of the human PVT across tissue-based and MRI-based approaches remains elusive, thereby limiting reliable translation between its cellular characteristics and in vivo functional connectivity. To address this challenge, we describe a histologically-informed PVT segmentation compatible with standard 3T MR imaging pipelines. We performed postmortem anatomical MRI scans on an intact whole brain and an excised thalamic block, manually segmented the PVT at high resolution using ex vivo calretinin staining and neuroanatomical landmarks, registered the resulting image-label pair to a commonly used MRI template space (Montreal Neurological Institutes MNI152), and performed a comparative reanalysis using this newly defined mask. This tissue-grounded PVT mask largely overlaps spatially with existing MRI-based PVT masks, with the exception of additional voxels posteriorly. Importantly, the functional connectivity patterns of this tissue-grounded mask are highly consistent with those previously reported. Collectively, this multimodal definition of the human PVT balances tissue-based ground truth with in vivo MRI features, providing a valuable resource for advancing translation between cellular level features identified by histology and in vivo functional connectivity at the meso/macro scale in the understudied human PVT. Key PointsO_LIAddresses conflict between histological and MRI-based borders of the human PVT. C_LIO_LIHistologically-defined PVT boundaries indicate additional posterior tail to the human PVT as compared to existing human MRI atlases. C_LIO_LIProvided MRI mask demonstrates functional connectivity patterns consistent with prior human and rodent studies. C_LI

neuroscience↗

bioRxiv2021

Distinct fastigial output channels and their impact on temporal lobe seizures

Despite being canonically considered a motor control structure, the cerebellum is increasingly recognized for important roles in processes beyond this traditional framework, including seizure suppression. Excitatory fastigial neurons project to a large number of downstream targets, and it is unclear if this broad targeting underlies seizure suppression, or if a specific output may be sufficient. To address this question, we used the intrahippocampal kainic acid mouse model of temporal lobe epilepsy, male and female animals, and a dual-virus approach to selectively label and manipulate fastigial outputs. We examined fastigial neurons projecting to the superior colliculus, medullary reticular formation, and central lateral nucleus of the thalamus, and found that these comprise largely non-overlapping populations of neurons which send collaterals to unique sets of additional thalamic and brainstem regions, creating distinct, somewhat overlapping, "output channels". We found that neither optogenetic stimulation of superior colliculus nor reticular formation output channels attenuated hippocampal seizures. In contrast, on-demand stimulation of fastigial neurons targeting the central lateral nucleus robustly inhibited seizures. Our results indicate that fastigial control of hippocampal seizures does not require simultaneous modulation of many fastigial output channels. Rather, selective modulation of the fastigial output channel to the central lateral thalamus, specifically, is sufficient for seizure control. This may provide a means for more selective therapeutic interventions, which provide seizure control while minimizing unwanted side effects. More broadly, our data highlight the concept of specific cerebellar output channels, whereby discrete cerebellar nucleus neurons project to specific aggregates of downstream targets, with distinct functional outcomes. Significance statementThe cerebellum has an emerging relationship with non-motor systems and may represent a powerful target for therapeutic intervention in temporal lobe epilepsy. We find that fastigial neurons project to numerous brain regions via largely segregated output channels, and that excitation of fastigial neurons projecting to the central lateral nucleus of the thalamus, but not the superior colliculus or reticular formation, is sufficient to attenuate hippocampal seizures. These findings illustrate an important conceptual framework: fastigial neurons project to aggregates of downstream targets via distinct output channels, which cannot be predicted simply by somatic location within the nucleus, and these channels have distinct functional outcomes. This nuanced appreciation of fastigial outputs may provide a path for therapeutic interventions with minimized side effects.

neuroscience↗

bioRxiv2019

A novel population of long-range inhibitory neurons

The hippocampus, a brain region important for spatial navigation and episodic memory, benefits from a rich diversity of neuronal cell-types. Recent work suggests fundamental gaps in our knowledge of these basic building blocks (i.e., neuronal types) in the hippocampal circuit, despite extensive prior examination. Through the use of an intersectional genetic viral vector approach, we report a novel hippocampal neuronal population, which has not previously been characterized, and which we refer to as LINCs. LINCs are GABAergic, but, in addition to broadly targeting local CA1 cells, also have long-range axons. LINCs are thus both interneurons and projection neurons. We demonstrate that LINCs, despite being relatively few in number, can have a strong influence on both hippocampal and extrahippocampal network synchrony and function. Identification and characterization of this novel cell population advances our basic understanding of both hippocampal circuitry and neuronal diversity.

neuroscience↗