Evidence for GABAergic projections from the tegmental nuclei of Gudden to the mammillary body in the rat
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Mammillary body
Tegmentum
Mammillary body
Tegmentum
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Muscimol
Disinhibition
Pedunculopontine Tegmental Nucleus
Tegmentum
Diencephalon
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Abstract Freezing is a conserved defensive behaviour that constitutes a major stress-coping mechanism. Decades of research have demonstrated a role of the amygdala, periaqueductal grey and hypothalamus as core actuators of the control of fear responses, including freezing. However, the role that other modulatory sites provide to this hardwired scaffold is not known. Here, we show that freezing elicited by exposure to electrical foot shocks activates laterodorsal tegmentum (LDTg) GABAergic neurons projecting to the VTA, without altering the excitability of cholinergic and glutamatergic LDTg neurons. Selective chemogenetic silencing of this inhibitory projection, but not other LDTg neuronal subtypes, dampens freezing responses but does not prevent the formation of conditioned fear memories. Conversely, optogenetic-activation of LDTg GABA terminals within the VTA drives freezing responses and elicits bradycardia, a common hallmark of freezing. Notably, this aversive information is subsequently conveyed from the VTA to the amygdala via a discrete GABAergic pathway. Hence, we unveiled a circuit mechanism linking LDTg-VTA-amygdala regions, which holds potential translational relevance for pathological freezing states such as post-traumatic stress disorders, panic attacks and social phobias.
Freezing behavior
Periaqueductal gray
Tegmentum
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The glutamatergic and GABAergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) mediated diverse brain functions. However, their whole-brain neural connectivity has not been comprehensively mapped. Here we used the virus tracers to characterize the whole-brain inputs and outputs of glutamatergic and GABAergic neurons in VTA and SNc. We found that these neurons received similar inputs from upstream brain regions, but some quantitative differences were also observed. Neocortex and dorsal striatum provided a greater share of input to VTA glutamatergic neurons. Periaqueductal gray and lateral hypothalamic area preferentially innervated VTA GABAergic neurons. Specifically, superior colliculus provided the largest input to SNc glutamatergic neurons. Compared to input patterns, the output patterns of glutamatergic and GABAergic neurons in the VTA and SNc showed significant preference to different brain regions. Our results laid the anatomical foundation for understanding the functions of cell-type-specific neurons in VTA and SNc.
Superior colliculus
Pars compacta
Pedunculopontine Tegmental Nucleus
Periaqueductal gray
Tegmentum
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Dopaminergic pathways
Mesolimbic pathway
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Abstract Evidence suggests that dopaminergic neurons of the ventral mesencephalic tegmentum (VMT) could be important for paradoxical sleep (PS). Here, we examined whether dopamine (DA) and adjacent γ‐aminobutyric acid (GABA)‐synthesizing neurons are active in association with PS recovery as compared to PS deprivation or control conditions in different groups of rats by using c‐Fos expression as a reflection of neural activity, combined with dual immunostaining for tyrosine hydroxylase (TH) or glutamic acid decarboxylase (GAD). Numbers of TH + /c‐Fos + neurons in the substantia nigra (SN) were not significantly different across groups, whereas those in the ventral tegmental area (VTA) were significantly different and greatest in PS recovery. Numbers of GAD + /c‐Fos + neurons in both VTA and SN were greatest in PS recovery. Thus, DA neuronal activity does not appear to be suppressed by local GABAergic neuronal activity during PS but might be altered in pattern by this inhibitory as well as other excitatory, particularly cholinergic, inputs such as to allow DA VTA neurons to become maximally active during PS and thereby contribute to the unique physiological and cognitive aspects of that state.
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Red nucleus
Dentate nucleus
Deep cerebellar nuclei
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Tegmentum
Pedunculopontine Tegmental Nucleus
Pars compacta
Superior colliculus
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Mesolimbic pathway
Dopaminergic pathways
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Abstract The substantia nigra pars compacta and the ventral tegmental area are part of a complex network in the basal ganglia involved in behaviours as diverse as motor planning, generation of pleasure and drug addiction. Here we report that in the dopaminergic neurons of the rat ventral midbrain a brief coactivation of group I metabotropic and NMDA glutamate receptors may transform a temporally dispersed synaptic GABAergic input into a rhythmic pattern (range 4.5–22.5 Hz), probably through a mechanism involving electrotonic couplings. The plastic and long‐lasting modification in the temporal code of the inhibitory synaptic activity induced by glutamate may be a key element in determining the function of midbrain dopaminergic neurons in both normal and pathological behaviour.
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