Chemical stimulation of the thalamic reticular nucleus inhibits the neuronal activity of the posterior insular cortex in rats

Extracellular neuronal responses were recorded from the posterior insular cortex following electrical and chemical stimulation of the thalamic reticular nucleus (Rt) regions. In the present study, most neurons (29/32) were first characterized for their responses to electrical stimulation of the superior laryngeal (SL) nerve or glossopharyngeal (IXth) nerve. In the first experiment, 15 neurons in the posterior insular cortex were examined for their responses to electrical stimulation of the Rt regions. It was found that effective stimulation sites to evoke action potentials in the posterior insular cortex were the ventromedial portion of the Rt and its adjacent regions. In the second experiment, 17 neurons in the posterior insular cortex were examined for their responses by pressure injection of glutamate (Glu) into the Rt regions. Of the 17 neurons, 13 were inhibited in the spontaneous discharge rate following injection of Glu into the Rt, and the remaining four were unaffected. Histologically, it was demonstrated that Glu injection sites for the case of inhibition were located near or within the Rt. On the other hand, the injection sites for all four non-responsive neurons were located outside of the Rt. These data suggest that excitation of the Rt (GABAergic neurons) causes depression of the neuronal activity in the thalamic relay nucleus and then this may in turn induce depressed neuronal activity in the posterior insular cortex. The results here indicate that neuronal activity in the posterior insular cortex is controlled by the Rt, which has been reported in other sensory systems.     

Generation of ventralized human thalamic organoids with thalamic reticular nucleus

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电刺激和损毁丘脑中央下核对大鼠福尔马林诱发伤害性行为的影响

本文旨在研究丘脑中央下核（thalamic nucleus submedius,Sm）是否参与持续伤害感受性调制。以自动运动检测系统记录大鼠一侧后爪皮下注射福尔马林诱发的伤害性行为（烦乱反应）为指标,观察电刺激和电解损毁Sm对烦乱反应的效应。结果显示,电刺激（100μA,5min）同侧或对侧Sm明显抑制福尔马林诱发的第二时相的烦乱反应,而刺激Sm外邻近结构（超过0．5mm）对烦乱反应无明显效应。电解损毁双侧Sm对第一或第二时相的烦乱反应均无影响。结果提示,Sm不仅参与急性时相性伤害感受性调制,也参与持续性伤害感受性调制。本研究为Sm参与下行痛调制提供了新的证据。     

An accessory prefrontal cortex–thalamus circuit sculpts maternal behavior in virgin female mice

The ability to care for the young is innate and readily displayed by postpartum females after delivery to ensure offspring survival. Upon pup exposure, rodent virgin (nulliparous) females also develop parental behavior that over time becomes displayed at levels equivalent to parenting mothers. Although maternal behavior in postpartum females and the associated neurocircuits are well characterized, the neural mechanisms underlying the acquisition of maternal behavior without prior experience remain poorly understood. Here, we show that the development of maternal care behavior in response to first‐time pup exposure in virgin females is initiated by the activation of the anterior cingulate cortex (ACC). ACC activity is dependent on feedback excitation by Vglut2⁺/Galanin⁺ neurons of the centrolateral nucleus of the thalamus (CL), with their activity sufficient to display parenting behaviors. Accordingly, acute bidirectional chemogenetic manipulation of neuronal activity in the ACC facilitates or impairs the attainment of maternal behavior, exclusively in virgin females. These results reveal an ACC‐CL neurocircuit as an accessory loop in virgin females for the initiation of maternal care upon first‐time exposure to pups.     

The facilitatory influence of anterior cingulate cortex on ON-OFF response of tactile neuron in thalamic ventrobasal nucleus

The structures of limbic system have been found to modulate the auditory, visual and pain afferent signals in the related nuclei of thalamus. One of those structures is anterior cingulate cortex (ACC) that influences nocuous response of the pain-sensitive neurons in the ventropostero-lateral nucleus of thalamus. Thus, we inferred that ACC would also modulate tactile information at the thalamic level. To test this assumption, single units were recorded extracellularly from thalamic ventrobasal nucleus (VB). Tactile ON-OFF response and the relationship between different patterns of the responses and the parameters of tactile stimulation were examined. Furthermore, the influence of ACC on the tactile ON-OFF response was studied. ACC stimulation was found to produce a facilitatory effect on the OFF-response of ON-OFF neurons. It lowered the threshold of the off-response of that neuron, and therefore changed the response pattern or enhanced the firing rate of the OFF-response of the neuron. The study on receptive fields of ON-OFF neurons showed that the excitation of the ACC could change an ON-response on the verge of a receptive field into an ON-OFF response. The above results suggest that the ACC modulation sharpens the response of a VB neuron to a moving stimulus within its receptive field, indicating that the limbic system can modulate tactile ascending sensory information.     

The facilitatory influence of anterior cingulate cortex on ON-OFF response of tactile neuron in thalamic ventrobasal nucleus

The structures of limbic system have been found to modulate the auditory, visual and pain afferent signals in the related nuclei of thalamus. One of those structures is anterior cingulate cortex (ACC) that influences nocuous response of the pain-sensitive neurons in the ventropos-tero-lateral nucleus of thalamus. Thus, we inferred that ACC would also modulate tactile information at the thalamic level. To test this assumption, single units were recorded extracellularly from thalamic ventrobasal nucleus (VB). Tactile ON-OFF response and the relationship between different patterns of the responses and the parameters of tactile stimulation were examined. Furthermore, the influence of ACC on the tactile ON-OFF response was studied. ACC stimulation was found to produce a facilitatory effect on the OFF-response of ON-OFF neurons. It lowered the threshold of the off-response of that neuron, and therefore changed the response pattern or enhanced the firing rate of the OFF-response of the neuron. The study on rec     

Differential effects of methylphenidate and cocaine on GABA transmission in sensory thalamic nuclei

Methylphenidate (MPH) is widely used to treat children and adolescents diagnosed with attention deficit/hyperactivity disorder. Although MPH shares mechanistic similarities to cocaine, its effects on GABAergic transmission in sensory thalamic nuclei are unknown. Our objective was to compare cocaine and MPH effects on GABAergic projections between thalamic reticular and ventrobasal (VB) nuclei. Mice (P18‐30) were subjected to binge‐like cocaine and MPH acute and sub‐chronic administrations. Cocaine and MPH enhanced hyperlocomotion, although sub‐chronic cocaine‐mediated effects were stronger than MPH effects. Cocaine and MPH sub‐chronic administration altered paired‐pulse and spontaneous GABAergic input differently. The effects of cocaine on evoked paired‐pulse GABA‐mediated currents changed from depression to facilitation with the duration of the protocols used, while MPH induced a constant increase throughout the administration protocols. Thalamic reticular nucleus GAD67 and VB Ca_V3.1 protein levels were measured using western blot to better understand their link to increased GABA release. Both proteins were increased by sub‐chronic administration of cocaine. MPH showed effects on GABAergic transmission that seems less disruptive than cocaine. Unique effects of cocaine on postsynaptic VB calcium currents might explain deleterious cocaine effects on sensory thalamic nuclei. These results suggest that cocaine and MPH produced distinct presynaptic alterations on GABAergic transmission.     

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLA^Glu) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLA^Glu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (IC^Glu) to BLA^Glu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MD^Glu) to BLA^Glu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund’s adjuvant (CFA) into their paws. Optical inhibition of the IC^Glu→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MD^Glu→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the IC^Glu→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MD^Glu→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete IC^Glu→BLA and MD^Glu→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.     

Deep brain stimulation of the accumbens increases dopamine,serotonin, and noradrenaline in the prefrontal cortex

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is effective in treatment‐refractory obsessive‐compulsive disorder and major depressive disorder. However, little is known about the neurobiological mechanisms underlying the rapid and effective changes of DBS. One of the hypotheses is that DBS modulates activity of monoamine neurotransmitters. In this study, we evaluated the effects of DBS in the NAc core on the extracellular concentration of monoaminergic neurotransmitters in the medial (mPFC) and orbital prefrontal cortex (OFC). Freely moving rats were bilaterally stimulated in the NAc core for 2 h while dopamine, serotonin, and noradrenaline were measured using in vivo microdialysis in the mPFC and the OFC. We report rapid increases in the release of dopamine and serotonin to a maximum of 177% and 127% in the mPFC and an increase up to 171% and 166% for dopamine and noradrenaline in the OFC after onset of stimulation in the NAc core. These results provide further evidence for the distal effects of DBS and corroborate previous clinical and pre‐clinical findings of altered neuronal activity in prefrontal areas.     

Control of the superior colliculus by the lateral prefrontal cortex

Several decades of patient, functional imaging and neurophysiological studies have supported a model in which the lateral prefrontal cortex (PFC) acts to suppress unwanted saccades by inhibiting activity in the oculomotor system. However, recent results from combined PFC deactivation and neural recordings of the superior colliculus in monkeys demonstrate that the primary influence of the PFC on the oculomotor system is excitatory, and stands in direct contradiction to the inhibitory model of PFC function. Although erroneous saccades towards a visual stimulus are commonly labelled reflexive in patients with PFC damage or dysfunction, the latencies of most of these saccades are outside of the range of express saccades, which are triggered directly by the visual stimulus. Deactivation and pharmacological manipulation studies in monkeys suggest that response errors following PFC damage or dysfunction are not the result of a failure in response suppression but can best be understood in the context of a failure to maintain and implement the proper task set.     

Environmental enrichment decreases cell surface expression of the dopamine transporter in rat medial prefrontal cortex

Rats raised in an enriched environmental condition (EC) exhibit a decreased (35%) maximal velocity (V(max)) of [3H]dopamine (DA) uptake in medial prefrontal cortex (mPFC) compared with rats raised in an impoverished condition (IC); however, no differences between EC and IC groups in V(max) for [3H]DA uptake were found in nucleus accumbens and striatum. Using biotinylation and immunoblotting techniques, the present study examined whether the brain region-specific decrease in DA transporter (DAT) function is the result of a reduction in DAT cell surface expression. In mPFC, nucleus accumbens and striatum, total DAT immunoreactivity was not different between EC and IC groups. Whereas no differences in cell surface expression of DAT were found in nucleus accumbens and striatum, DAT immunoreactivity in the biotinylated cell surface fraction of mPFC was decreased (39%) in EC compared with IC rats, consistent with the magnitude of the previously observed decrease in V(max) for [3H]DA uptake in mPFC in EC rats. These results suggest that the decrease in DAT cell surface expression in the mPFC may be responsible for decreased DAT function in the mPFC of EC compared with IC rats, and that there is plasticity in the regulatory mechanisms mediating DAT trafficking and function.     

NMDA-mediated modulation of dopamine release is modified in rat prefrontal cortex and nucleus accumbens after chronic nicotine treatment

In this study, we investigate the effects of chronic administration of (−)nicotine on the function of the NMDA-mediated modulation of [³H]dopamine (DA) release in rat prefrontal cortex (PFC) and nucleus accumbens (NAc). In the PFC synaptosomes NMDA in a concentration-dependent manner evoked [³H]DA release in rats chronically treated with vehicle (14 days) with an EC₅₀ of 13.1 ± 2.0 μM. The NMDA-evoked overflow of the [³H]DA in PFC nerve endings of rats treated with (−)nicotine was significantly lower (−43%) than in vehicle treated rats. The EC₅₀ was 9.0 ± 1.4 μM. Exposure of NAc synaptosomes of rats treated with vehicle to NMDA produced an increase in [³H]DA overflow with an EC₅₀ of 14.5 ± 5.5 μM. This effect was significantly enhanced in chronically treated animals. The EC₅₀ was 10.5 ± 0.5 μM. The K⁺-evoked release of [³H]DA was not modified by the (−)nicotine administration. Both the changes of the NMDA-evoked [³H]DA overflow in the NAc and PFC disappeared after 14 days withdrawal. The results show that chronic (−)nicotine differentially affects the NMDA-mediated [³H]DA release in the PFC and NAc of the rat.     

Feedback Inhibition and Throughput Properties of an Integrate-and-Fire-or-Burst Network Model of Retinogeniculate Transmission

Computational modeling has played an important role in the dissection of the biophysical basis of rhythmic oscillations in thalamus that are associated with sleep and certain forms of epilepsy. In contrast, the dynamic filter properties of thalamic relay nuclei during states of arousal are not well understood. Here we present a modeling and simulation study of the throughput properties of the visually driven dorsal lateral geniculate nucleus (dLGN) in the presence of feedback inhibition from the perigeniculate nucleus (PGN). We employ thalamocortical (TC) and thalamic reticular (RE) versions of a minimal integrate-and-fire-or-burst type model and a one-dimensional, two-layered network architecture. Potassium leakage conductances control the neuromodulatory state of the network and eliminate rhythmic bursting in the presence of spontaneous input (i.e., wake up the network). The aroused dLGN/PGN network model is subsequently stimulated by spatially homogeneous spontaneous retinal input or spatio-temporally patterned input consistent with the activity of X-type retinal ganglion cells during full-field or drifting grating visual stimulation. The throughput properties of this visually-driven dLGN/PGN network model are characterized and quantified as a function of stimulus parameters such as contrast, temporal frequency, and spatial frequency. During low-frequency oscillatory full-field stimulation, feedback inhibition from RE neurons often leads to TC neuron burst responses, while at high frequency tonic responses dominate. Depending on the average rate of stimulation, contrast level, and temporal frequency of modulation, the TC and RE cell bursts may or may not be phase-locked to the visual stimulus. During drifting-grating stimulation, phase-locked bursts often occur for sufficiently high contrast so long as the spatial period of the grating is not small compared to the synaptic footprint length, i.e., the spatial scale of the network connectivity.     

Hierarchical action encoding in prefrontal cortex of freely moving macaques

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Catecholamine release and uptake in the mouse prefrontal cortex

Monitoring the release and uptake of catecholamines from terminals in weakly innervated brain regions is an important step in understanding their importance in normal brain function. To that end, we have labeled brain slices from transgenic mice that synthesize placental alkaline phosphatase (PLAP) on neurons containing tyrosine hydroxylase with antibody-fluorochrome conjugate, PLAP-Cy5. Excitation of the fluorochrome enables catecholamine neurons to be visualized in living tissue. Immunohistochemical fluorescence with antibodies to tyrosine hydroxylase and dopamine beta-hydroxylase revealed that the PLAP labeling was specific to catecholamine neurons. In the prefrontal cortex (PFC), immunohistochemical fluorescence of the PLAP along with staining for dopamine transporter (DAT) and norepinephrine transporter (NET) revealed that all three exhibit remarkable spatial overlap. Fluorescence from the PLAP antibody was used to position carbon-fiber microelectrodes adjacent to catecholamine neurons in the PFC. Following incubation with L-DOPA, catecholamine release and subsequent uptake was measured and the effect of uptake inhibitors examined. Release and uptake in NET and DAT knockout mice were also monitored. Uptake rates in the cingulate and prelimbic cortex are so slow that catecholamines can exist in the extracellular fluid for sufficient time to travel approximately 100 microm. The results support heterologous uptake of catecholamines and volume transmission in the PFC of mice.     

6-OHDA毁损黑质致密部对大鼠PPN和VL神经元放电活动的影响

目的：观察6-羟多巴胺单侧毁损黑质致密部多巴胺神经元后,脚桥核（PPN）和丘脑腹外侧核（VL）神经元自发放电活动的变化,探讨帕金森病（PD）的发病机制。方法：应用玻璃微电极细胞外记录法,观察对照组和PD组PPN和VL神经元的放电频率和放电形式的变化。结果：对照组和PD组大鼠PPN放电频率分别为（8．31±0．62）Hz和（10．70±0．85）Hz,PD组放电频率明显高于对照组（P〈0．05）。和对照组相比,PD组PPN的不规则和爆发式放电神经元构成比例明显增多（P〈0．01）,同时规则放电频率增加（P〈0．01）。对照组和PD组大鼠VL的放电频率分别为（6．25±0．54）Hz和（5．67±0．46）Hz,两组间没有显著性差异。VL神经元放电形式表现为不规则和爆发式放电,两组间构成比也没有明显差异,但PD组爆发式神经元放电频率明显降低（P〈0．01）。结论：PD状态下,PPN神经元活动增强,PPN可能参与了PD的病理生理过程,VL神经元放电可能受PPN神经元投射的调节。