Laterodorsal Tegmentum and Pedunculopontine Tegmental Nucleus Circuits Regulate Renal Functions: Neuroanatomical Evidence in Mice Models

Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.

Prenatal nicotine alters development of the laterodorsal tegmentum:Possible role for attention-deficit/hyperactivity disorder and drug dependence

As we cycle between the states of wakefulness and sleep,a bilateral cholinergic nucleus in the pontine brain stem,the laterodorsal tegmentum(LDT),plays a critical role in controlling salience processing,attention,behavioral arousal,and electrophysiological signatures of the sub-and microstates of sleep.Disorders involving abnormal alterations in behavioral and motivated states,such as drug dependence,likely involve dysfunctions in LDT signaling.In addition,as the LDT exhibits connectivity with the thalamus and mesocortical circuits,as well as receives direct,excitatory input from the prefrontal cortex,a role for the LDT in cognitive symptoms characterizing attention-deficit/hyperactivity disorder(ADHD)including impulsivity,inflexibility,and dysfunctions of attention is suggested.Prenatal nicotine exposure(PNE)is associated with a higher risk for later life development of drug dependence and ADHD,suggesting alteration in development of brain regions involved in these behaviors.PNE has been shown to alter glutamate and cholinergic signaling within the LDT.As glutamate and acetylcholine are major excitatory mediators,these alterations would likely alter excitatory output to target regions in limbic motivational circuits and to thalamic and cortical networks mediating executive control.Further,PNE alters neuronal development and transmission within prefrontal cortex and limbic areas that send input to the LDT,which would compound effects of differential processing within the PNE LDT.When taken together,alterations in signaling in the LDT are likely to play a role in negative behavioral outcomes seen in PNE individuals,including a heightened risk of drug dependence and ADHD behaviors.

Brain-wide Mapping of Mono-synaptic Afferents to Different Cell Types in the Laterodorsal Tegmentum

The laterodorsal tegmentum(LDT) is a brain structure involved in distinct behaviors including arousal,reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains unclear.Using a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex(VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive(PV?) GABAergic cells received preferential projections from local LDT neurons.With regard to the different subtypes of GABAergic cells, aconsiderable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatinpositive cells than to PV?cells. Diverse inputs to the LDT on a system-wide level were revealed.

Effects of acupuncture stimulation of the sacral region on EEG and urinary bladder activity in rats

Objective To observe the effect of acupuncture stimulation of the sacral segment on the excitability of the cerebral cortex and the activity of the urinary bladder and the involvement of the cholinergic neurons in the laterodorsal tegmental （LDT） nucleus of the brainstem in acupuncture-induced electroencephalogram （EEG） changes. Methods A total of 109 SD rats were used in the present study. Under anesthesia （urethane）, a pair of stainless steel electrodes was separately implanted into the frontal and parietal bony sutures to record EEG. Glass microelectrodes were used to record extracellular discharges of single neuron of the LDT nucleus in the brainstem. Urinary bladder pressure was recorded through a catheter inserted in the bladder and the contraction was induced by infusion of normal saline. A filiform acupuncture needle was inserted into the sacral segment Ecorresponding to Zhongliao （中髎BL 33）] and rotated manually for 1 min. Results In 27 rats whose bladder was full of normal saline, acupuncture stimulation of the sacral region suppressed the contraction activity of the bladder, the fast EEG with lower amplitude and higher frequency tuned into slow EEG with higher amplitude and lower frequency in 6 cases （22.2%）. The inhibitory effect occurred from 45 s to 12 min after acupuncture manipulation. In 82 rats whose bladder was empty, acupuncture stimulation caused the fast EEG to turn into slow EEG in 71 cases （86.6%）. Simultaneously, LDT cholinergic neurons reduced their firing rates from （2.9±1.5） Hz to （1.2±0.6） Hz （n = 12, P〈0.05）, and the reduction of LDT neuronal discharge was earlier in time than the change of EEG. Conclusion Acupuncture stimulation of the sacral region can lower the excitability of the cerebral cortex and suppress bladder activity, which is closely associated with its resultant inhibitory effect on the electrical activity of LDT cholinergic neurons.