Serotonin activates paraventricular thalamic neurons through direct depolarization and indirect disinhibition from Zona Incerta

AbstractFear generalization and deficits in extinction learning are debilitating dimensions of Post-Traumatic Stress Disorder (PTSD). Most understanding of the neurobiology underlying these dimensions comes from studies of cortical and limbic brain regions. While thalamic and subthalamic regions have been implicated in modulating fear, the potential for incerto-thalamic pathways to suppress fear generalization and rescue deficits in extinction recall remains unexplored. We first used patch-clamp electrophysiology to examine functional connections between the subthalamic zona incerta and thalamic reuniens (RE). Optogenetic stimulation of GABAergic ZI → RE cell terminals in vitro induced inhibitory post-synaptic currents (IPSCs) in the RE. We then combined high-intensity discriminative auditory fear conditioning with cell-type-specific and projection-specific optogenetics in mice to assess functional roles of GABAergic ZI → RE cell projections in modulating fear generalization and extinction recall. In addition, we used a similar approach to test the possibility of fear generalization and extinction recall being modulated by a smaller subset of GABAergic ZI → RE cells, the A13 dopaminergic cell population. Optogenetic stimulation of GABAergic ZI → RE cell terminals attenuated fear generalization and enhanced extinction recall. In contrast, optogenetic stimulation of dopaminergic ZI → RE cell terminals had no effect on fear generalization but enhanced extinction recall in a dopamine receptor D1-dependent manner. Our findings shed new light on the neuroanatomy and neurochemistry of ZI-located cells that contribute to adaptive fear by increasing the precision and extinction of learned associations. In so doing, these data reveal novel neuroanatomical substrates that could be therapeutically targeted for treatment of PTSD.

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Neurons in the lateral hypothalamic area and zona incerta with ascending projections to the subfornical organ area in the rat

Brain Research ◽

10.1016/0006-8993(88)90247-8 ◽

1988 ◽

Vol 456 (2) ◽

pp. 397-400 ◽

Cited By ~ 14

Author(s):

Junichi Tanaka ◽

Katsuo Seto

Keyword(s):

Subfornical Organ ◽

Lateral Hypothalamic Area ◽

Zona Incerta ◽

Hypothalamic Area ◽

Lateral Hypothalamic

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The zona incerta modulates spontaneous spike-wave discharges in the rat

Journal of Neurophysiology ◽

10.1152/jn.00750.2011 ◽

2013 ◽

Vol 109 (10) ◽

pp. 2505-2516 ◽

Cited By ~ 8

Author(s):

Fu-Zen Shaw ◽

Yi-Fang Liao ◽

Ruei-Feng Chen ◽

Yu-Hsing Huang ◽

Rick C. S. Lin

Keyword(s):

Functional Role ◽

Significant Inhibition ◽

Zona Incerta ◽

Obvious Effect ◽

Spike Wave Discharges ◽

Long Evans ◽

Oscillation Frequencies ◽

Spike Wave ◽

Stimulation Of

The contribution of the zona incerta (ZI) of the thalamus on spike-wave discharges (SWDs) was investigated. Chronic recordings of bilateral cortices, bilateral vibrissa muscle, and unilateral ZI were performed in Long-Evans rats to examine the functional role of SWDs. Rhythmic ZI activity appeared at the beginning of SWD and was accompanied by higher-oscillation frequencies and larger spike magnitudes. Bilateral lidocaine injections into the mystacial pads led to a decreased oscillation frequency of SWDs, but the phenomenon of ZI-related spike magnitude enhancement was preserved. Moreover, 800-Hz ZI microstimulation terminates most of the SWDs and whisker twitching (WT; >80%). In contrast, 200-Hz ZI microstimulation selectively stops WTs but not SWDs. Stimulation of the thalamic ventroposteriomedial nucleus showed no obvious effect on terminating SWDs. A unilateral ZI lesion resulted in a significant reduction of 7- to 12-Hz power of both the ipsilateral cortical and contralateral vibrissae muscle activities during SWDs. Intraincertal microinfusion of muscimol showed a significant inhibition on SWDs. Our present data suggest that the ZI actively modulates the SWD magnitude and WT behavior.

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Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons

Communications Biology ◽

10.1038/s42003-020-01616-7 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Dong Won Kim ◽

Kai Liu ◽

Zoe Qianyi Wang ◽

Yi Stephanie Zhang ◽

Abhijith Bathini ◽

...

Keyword(s):

Cortical Neurons ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Gabaergic Neurons ◽

Zona Incerta ◽

Long Distance ◽

Hypothalamic Neurons ◽

Cortical Interneuron ◽

Tangential Migration ◽

Innate Behaviors

AbstractGABAergic neurons of the hypothalamus regulate many innate behaviors, but little is known about the mechanisms that control their development. We previously identified hypothalamic neurons that express the LIM homeodomain transcription factor Lhx6, a master regulator of cortical interneuron development, as sleep-promoting. In contrast to telencephalic interneurons, hypothalamic Lhx6 neurons do not undergo long-distance tangential migration and do not express cortical interneuronal markers such as Pvalb. Here, we show that Lhx6 is necessary for the survival of hypothalamic neurons. Dlx1/2, Nkx2-2, and Nkx2-1 are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons, and that Nkx2-2+/Lhx6+ neurons of the zona incerta are responsive to sleep pressure. We further identify multiple neuropeptides that are enriched in spatially segregated subsets of hypothalamic Lhx6 neurons, and that are distinct from those seen in cortical neurons. These findings identify common and divergent molecular mechanisms by which Lhx6 controls the development of GABAergic neurons in the hypothalamus.

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Coronal Gradient Echo MRI to Visualize the Zona Incerta for Deep Brain Stimulation Targeting in Parkinson’s Disease

Stereotactic and Functional Neurosurgery ◽

10.1159/000515772 ◽

2021 ◽

pp. 1-8

Author(s):

Ashesh A. Thaker ◽

Kartik M. Reddy ◽

John A. Thompson ◽

Pamela David Gerecht ◽

Mark S. Brown ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Regions Of Interest ◽

Zona Incerta ◽

Gradient Echo ◽

Noise Ratio ◽

Deep Brain

Introduction: Deep brain stimulation of the zona incerta is effective at treating tremor and other forms of parkinsonism. However, the structure is not well visualized with standard MRI protocols making direct surgical targeting unfeasible and contributing to inconsistent clinical outcomes. In this study, we applied coronal gradient echo MRI to directly visualize the rostral zona incerta in Parkinson’s disease patients to improve targeting for deep brain stimulation. Methods: We conducted a prospective study to optimize and evaluate an MRI sequence to visualize the rostral zona incerta in patients with Parkinson’s disease (n = 31) and other movement disorders (n = 13). We performed a contrast-to-noise ratio analysis of specific regions of interest to quantitatively assess visual discrimination of relevant deep brain structures in the optimized MRI sequence. Regions of interest were independently assessed by 2 neuroradiologists, and interrater reliability was assessed. Results: Rostral zona incerta and subthalamic nucleus were well delineated in our 5.5-min MRI sequence, indicated by excellent interrater agreement between neuroradiologists for region-of-interest measurements (>0.90 intraclass coefficient). Mean contrast-to-noise ratio was high for both rostral zona incerta (6.39 ± 3.37) and subthalamic nucleus (17.27 ± 5.61) relative to adjacent white matter. There was no significant difference between mean signal intensities or contrast-to-noise ratio for Parkinson’s and non-Parkinson’s patients for either structure. Discussion/Conclusion: Our optimized coronal gradient echo MRI sequence delineates subcortical structures relevant to traditional and novel deep brain stimulation targets, including the zona incerta, with high contrast-to-noise. Future studies will prospectively apply this sequence to surgical planning and postimplantation outcomes.

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Organization of the zona incerta in the macaque: A nissl and golgi study

The Journal of Comparative Neurology ◽

10.1002/cne.903200302 ◽

1992 ◽

Vol 320 (3) ◽

pp. 273-290 ◽

Cited By ~ 30

Author(s):

Terence P. Ma ◽

Xiao-Jiang Hu ◽

Yakir Anavi ◽

Jos� A. Rafols

Keyword(s):

Zona Incerta ◽

Golgi Study

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Thalamic Neurons in the Pigeon Compute Distance-to-Collision of an Approaching Surface

Brain Behavior and Evolution ◽

10.1159/000145716 ◽

2008 ◽

Vol 72 (1) ◽

pp. 37-47 ◽

Cited By ~ 12

Author(s):

Rui-Feng Liu ◽

Yu-Qiong Niu ◽

Shu-Rong Wang

Keyword(s):

Thalamic Neurons

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SCALING BEHAVIOR OF THE DENDRITIC BRANCHES OF THALAMIC NEURONS

Fractals ◽

10.1142/s0218348x93000186 ◽

1993 ◽

Vol 01 (02) ◽

pp. 171-178 ◽

Cited By ~ 10

Author(s):

KLAUS-D. KNIFFKI ◽

MATTHIAS PAWLAK ◽

CHRISTIANE VAHLE-HINZ

Keyword(s):

Growth Process ◽

Scaling Law ◽

Branching Ratio ◽

Scaling Behavior ◽

Neuronal Growth ◽

Thalamic Neurons ◽

Dendritic Trees ◽

Ventrobasal Complex ◽

Dendritic Branches

The morphology of Golgi-impregnated thalamic neurons was investigated quantitatively. In particular, it was sought to test whether the dendritic bifurcations can be described by the scaling law (d0)n=(d1)n+(d2)nwith a single value of the diameter exponent n. Here d0 is the diameter of the parent branch, d1 and d2 are the diameters of the two daughter branches. Neurons from two functionally distinct regions were compared: the somatosensory ventrobasal complex (VB) and its nociceptive ventral periphery (VBvp). It is shown that for the neuronal trees studied in both regions, the scaling law was fulfilled. The diameter exponent n, however, was not a constant. It increased from n=1.76 for the 1st order branches to n=3.92 for the 7th order branches of neurons from both regions. These findings suggest that more than one simple intrinsic rule is involved in the neuronal growth process, and it is assumed that the branching ratio d0/d1 is not required to be encoded genetically. Furthermore, the results support the concept of the dendritic trees having a statistically identical topology in neurons of VB and VBvp and thus may be regarded as integrative modules.

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