Heterogeneity and Diversity of Striatal GABAergic Interneurons: Update 2018.

Our original review, "Heterogeneity and Diversity of Striatal GABAergic Interneurons," to which this is an invited update, was published in December, 2010 in Frontiers is Neuroanatomy. In that article, we reviewed several decades' worth of anatomical and electrophysiological data on striatal parvalbumin (PV)-, neuropeptide Y (NPY)- and calretinin(CR)-expressing GABAergic interneurons from many laboratories including our own. In addition, we reported on a recently discovered novel tyrosine hydroxylase (TH) expressing GABAergic interneuron class first revealed in transgenic TH EGFP reporter mouse line. In this review, we report on further advances in the understanding of the functional properties of previously reported striatal GABAergic interneurons and their synaptic connections. With the application of new transgenic fluorescent reporter and Cre-driver/reporter lines, plus optogenetic, chemogenetic and viral transduction methods, several additional subtypes of novel striatal GABAergic interneurons have been discovered, as well as the synaptic networks in which they are embedded. These findings make it clear that previous hypotheses in which striatal GABAergic interneurons modulate and/or control the firing of spiny neurons principally by simple feedforward and/or feedback inhibition are at best incomplete. A more accurate picture is one in which there are highly selective and specific afferent inputs, synaptic connections between different interneuron subtypes and spiny neurons and among different GABAergic interneurons that result in the formation of functional networks and ensembles of spiny neurons.

Role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of gastric cancer.

Patients with peritoneal carcinomatosis (PC) of gastric origin have a poor prognosis of life with an average survival of 1-3 months. Systemic chemotherapy has improved the survival of those patients with gastric metastatic cancer at 7-10 months. However, this benefit could not be reproduced in those patients with PC. The current literature for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) for gastric PC has significant variation related to patient selection, treatment intent (palliative vs. attempt at curative treatment), surgical technique, intraperitoneal chemotherapy agent utilized, and systemic chemotherapy administered adjuvantly. From the perspective of patient selection for cytoreduction and HIPEC, patients with extensive PC are not candidates. In addition, unresectable location would make a patient a poor candidate for cytoreduction and HIPEC. Optimally, those with positive peritoneal cytology alone could benefit most. However, the role of cytoreductive surgery and HIPEC in patients with PC of gastric origin has not yet been clarified.

Los pacientes con carcinomatosis peritoneal (CP) de origen gástrico tienen un mal pronóstico de vida, con una supervivencia media de 1 a 3 meses. La quimioterapia sistémica ha mejorado la supervivencia de los pacientes con cáncer gástrico metastásico a los 7-10 meses. Sin embargo, este beneficio no se ha podido reproducir en los pacientes con CP. En cuanto a lo relacionado con la literatura actual para el uso de HIPEC (hyperthermic intraperitoneal chemotherapy) en la CP de origen gástrico, existe una variación significativa en la selección de pacientes, la intención de tratamiento (paliativo frente a intento de tratamiento curativo), la técnica quirúrgica, el agente quimioterapéutico intraperitoneal utilizado y la quimioterapia sistémica adyuvante administrada. Desde la perspectiva de la selección de pacientes para citorreducción y tratamiento con HIPEC, los pacientes con CP extensa no son candidatos. Además, lesiones irresecables por su localización harían al paciente un pobre candidato para citorreducción y tratamiento con HIPEC. De manera óptima, aquellos pacientes con citología peritoneal positiva en ausencia de CP son quienes más podrían beneficiarse. Sin embargo, el papel de la cirugía citorreductora y del tratamiento con HIPEC en los pacientes con CP de origen gástrico aún no ha sido esclarecido.

Activation of Glutamatergic Fibers in the Anterior NAc Shell Modulates Reward Activity in the aNAcSh, the Lateral Hypothalamus, and Medial Prefrontal Cortex and Transiently Stops Feeding.

Although the release of mesoaccumbal dopamine is certainly involved in rewarding responses, recent studies point to the importance of the interaction between it and glutamate. One important component of this network is the anterior nucleus accumbens shell (aNAcSh), which sends GABAergic projections into the lateral hypothalamus (LH) and receives extensive glutamatergic inputs from, among others, the medial prefrontal cortex (mPFC). The effects of glutamatergic activation of aNAcSh on the ingestion of rewarding stimuli as well as its effect in the LH and mPFC are not well understood. Therefore, we studied behaving mice that express a light-gated channel (ChR2) in glutamatergic fibers in their aNAcSh while recording from neurons in the aNAcSh, or mPFC or LH. In Thy1-ChR2, but not wild-type, mice activation of aNAcSh fibers transiently stopped the mice licking for sucrose or an empty sipper. Stimulation of aNAcSh fibers both activated and inhibited single-unit responses aNAcSh, mPFC, and LH, in a manner that maintains firing rate homeostasis. One population of licking-inhibited pMSNs in the aNAcSh was also activated by optical stimulation, suggesting their relevance in the cessation of feeding. A rewarding aspect of stimulation of glutamatergic inputs was found when the Thy1-ChR2 mice learned to nose-poke to self-stimulate these inputs, indicating that bulky stimulation of these fibers are rewarding in the sense of wanting. Stimulation of excitatory afferents evoked both monosynaptic and polysynaptic responses distributed in the three recorded areas. In summary, we found that activation of glutamatergic aNAcSh fibers is both rewarding and transiently inhibits feeding. SIGNIFICANCE STATEMENT: We have established that the activation of glutamatergic fibers in the anterior nucleus accumbens shell (aNAcSh) transiently stops feeding and yet, because mice self-stimulate, is rewarding in the sense of wanting. Moreover, we have characterized single-unit responses of distributed components of a hedonic network (comprising the aNAcSh, medial prefrontal cortex, and lateral hypothalamus) recruited by activation of glutamatergic aNAcSh afferents that are involved in encoding a positive valence signal important for the wanting of a reward and that transiently stops ongoing consummatory actions, such as licking.

Primary retroperitoneal Merkel cell carcinoma: Case report and literature review.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that affects elderly patients and typically arises in sun-exposed skin. The disease is very rare and only few cases present with no apparent skin lesion. In the retroperitoneum there are only two cases reported in the literature. CASE PRESENTATION: We report a case of a 54-year-old Mexican male with MCC, which presented as a large retroperitoneal mass. Pathological and immunohistochemical analysis of the transabdominal CT-guided biopsy specimen revealed a MCC. The patient underwent preoperative chemotherapy followed by a laparotomy and the mass was successfully excised. DISCUSSION: There are two possible explanations for what occurred in our patient. The most plausible theory is the retroperitoneal mass could be a massively enlarged lymph node where precursor cells became neoplastic. This would be consistent with a presumptive diagnosis of primary nodal disease. Moreover, metastasis to the retroperitoneal lymph nodes has been reported as relatively common when compared to other sites such as liver, bone, brain and skin. The less probable theory is the non-described "regression" phenomena of a cutaneous MCC, but we are not found a primary skin lesion. CONCLUSION: Preoperative chemotherapy and excision of the primary tumor is the surgical treatment of choice for retroperitoneal MCC. We propose that further studies are needed to elucidate the true efficacy of chemotherapy in conventional and unconventional patients with MCC.

Are striatal tyrosine hydroxylase interneurons dopaminergic?

Striatal GABAergic interneurons that express the gene for tyrosine hydroxylase (TH) have been identified previously by several methods. Although generally assumed to be dopaminergic, possibly serving as a compensatory source of dopamine (DA) in Parkinson's disease, this assumption has never been tested directly. In TH-Cre mice whose nigrostriatal pathway had been eliminated unilaterally with 6-hydroxydopamine, we injected a Cre-dependent virus coding for channelrhodopsin-2 and enhanced yellow fluorescent protein unilaterally into the unlesioned midbrain or bilaterally into the striatum. Fast-scan cyclic voltammetry in striatal slices revealed that both optical and electrical stimulation readily elicited DA release in control striata but not from contralateral striata when nigrostriatal neurons were transduced. In contrast, neither optical nor electrical stimulation could elicit striatal DA release in either the control or lesioned striata when the virus was injected directly into the striatum transducing only striatal TH interneurons. This demonstrates that striatal TH interneurons do not release DA. Fluorescence immunocytochemistry in enhanced green fluorescent protein (EGFP)-TH mice revealed colocalization of DA, l-amino acid decarboxylase, the DA transporter, and vesicular monoamine transporter-2 with EGFP in midbrain dopaminergic neurons but not in any of the striatal EGFP-TH interneurons. Optogenetic activation of striatal EGFP-TH interneurons produced strong GABAergic inhibition in all spiny neurons tested. These results indicate that striatal TH interneurons are not dopaminergic but rather are a type of GABAergic interneuron that expresses TH but none of the other enzymes or transporters necessary to operate as dopaminergic neurons and exert widespread GABAergic inhibition onto direct and indirect spiny neurons.

Dopaminergic and cholinergic modulation of striatal tyrosine hydroxylase interneurons.

The recent electrophysiological characterization of TH-expressing GABAergic interneurons (THINs) in the neostriatum revealed an unexpected degree of diversity of interneurons in this brain area (Ibáñez-Sandoval et al., 2010, Unal et al., 2011, 2015). Despite being relatively few in number, THINs may play a significant role in transmitting and distributing extra- and intrastriatal neuromodulatory signals in the striatal circuitry. Here we investigated the dopaminergic and cholinergic regulation of THINs in vitro. We found that the dominant effect of dopamine was a dramatic enhancement of the ability of THINs to generate long-lasting depolarizing plateau potentials (PPs). Interestingly, the same effect could also be elicited by amphetamine-induced release of endogenous dopamine suggesting that THINs may exhibit similar responses to changes in extracellular dopamine concentration in vivo. The enhancement of PPs in THINs is perhaps the most pronounced effect of dopamine on the intrinsic excitability of neostriatal neurons described to date. Further, we demonstrate that all subtypes of THINSs tested also express nicotinic cholinergic receptors. All THIS responded, albeit differentially, with depolarization, PPs and spiking to brief application of nicotinic agonists. Powerful modulation of the nonlinear integrative properties of THINs by dopamine and the direct depolarization of these neurons by acetylcholine may play important roles in mediating the effects of these neuromodulators in the neostriatum with potentially important implications for understanding the mechanisms of neuropsychiatric disorders affecting the basal ganglia.

GABAergic circuits mediate the reinforcement-related signals of striatal cholinergic interneurons.

Neostriatal cholinergic interneurons are believed to be important for reinforcement-mediated learning and response selection by signaling the occurrence and motivational value of behaviorally relevant stimuli through precisely timed multiphasic population responses. An important problem is to understand how these signals regulate the functioning of the neostriatum. Here we describe the synaptic organization of a previously unknown circuit that involves direct nicotinic excitation of several classes of GABAergic interneurons, including neuroptide Y-expressing neurogilaform neurons, and enables cholinergic interneurons to exert rapid inhibitory control of the activity of projection neurons. We also found that, in vivo, the dominant effect of an optogenetically reproduced pause-excitation population response of cholinergic interneurons was powerful and rapid inhibition of the firing of projection neurons that is coincident with synchronous cholinergic activation. These results reveal a previously unknown circuit mechanism that transmits reinforcement-related information of ChAT interneurons in the mouse neostriatal network.

Neuron-specific effects of interleukin-1ß are mediated by a novel isoform of the IL-1 receptor accessory protein.

In the CNS, interleukin-1ß (IL-1ß) is synthesized and released during injury, infection, and disease, mediating inflammatory responses. However, IL-1ß is also present in the brain under physiological conditions, and can influence hippocampal neuronal function. Several cell-specific IL-1-mediated signaling pathways and functions have been identified in neurons and astrocytes, but their mechanisms have not been fully defined. In astrocytes, IL-1ß induced both the p38 MAPK and NF-κB (nuclear factor κB) pathways regulating inflammatory responses, however in hippocampal neurons IL-1ß activated p38 but not NF-κB. Additionally, IL-1ß induced Src phosphorylation at 0.01 ng/ml in hippocampal neurons, a dose 1000-fold lower than that used to stimulate inflammatory responses. IL-1 signaling requires the type 1 IL-1 receptor and the IL-1 receptor accessory protein (IL-1RAcP) as a receptor partner. We previously reported a novel isoform of the IL-1RAcP, IL-1RAcPb, found exclusively in CNS neurons. In this study, we demonstrate that AcPb specifically mediates IL-1ß activation of p-Src and potentiation of NMDA-induced calcium influx in mouse hippocampal neurons in a dose-dependent manner. Mice lacking the AcPb, but retaining the AcP, isoform were deficient in IL-1ß regulation of p-Src in neurons. AcPb also played a modulatory role in the activation of p38 MAPK, but had no effect on NF-κB signaling. The restricted expression of AcPb in CNS neurons, therefore, governs specific neuronal signaling and functional responses to IL-1ß.

A novel functionally distinct subtype of striatal neuropeptide Y interneuron.

We investigated the properties of neostriatal neuropeptide Y (NPY)-expressing interneurons in transgenic GFP (green fluorescent protein)-NPY reporter mice. In vitro whole-cell recordings and biocytin staining demonstrated the existence of a novel class of neostriatal NPY-expressing GABAergic interneurons that exhibit electrophysiological, neurochemical, and morphological properties strikingly different from those of previously described NPY-containing, plateau-depolarization low-threshold spike (NPY-PLTS) interneurons. The novel NPY interneuron type (NPY-neurogliaform) differed from previously described NPY-PLTS interneurons by exhibiting a significantly lower input resistance and hyperpolarized membrane potential, regular, nonaccommodating spiking in response to depolarizing current injections, and an absence of plateau depolarizations or low-threshold spikes. NPY-neurogliaform interneurons were also easily distinguished morphologically by their dense, compact, and highly branched dendritic and local axonal arborizations that contrasted sharply with the sparse and extended axonal and dendritic arborizations of NPY-PLTS interneurons. Furthermore, NPY-neurogliaform interneurons did not express immunofluorescence for somatostatin or nitric oxide synthase that was ubiquitous in NPY-PLTS interneurons. IPSP/Cs could only rarely be elicited in spiny projection neurons (SPNs) in paired recordings with NPY-PLTS interneurons. In contrast, the probability of SPN innervation by NPY-neurogliaform interneurons was extremely high, the synapse very reliable (no failures were observed), and the resulting postsynaptic response was a slow, GABA(A) receptor-mediated IPSC that has not been previously described in striatum but that has been elicited from NPY-GABAergic neurogliaform interneurons in cortex and hippocampus. These properties suggest unique and distinctive roles for NPY-PLTS and NPY-neurogliaform interneurons in the integrative properties of the neostriatum.

Distribution of tyrosine hydroxylase-expressing interneurons with respect to anatomical organization of the neostriatum.

We have recently shown in vitro that striatal tyrosine hydroxylase-expressing interneurons identified in transgenic mice by expression of enhanced green fluorescent protein (TH-eGFP) display electrophysiological profiles that are distinct from those of other striatal interneurons. Furthermore, striatal TH-eGFP interneurons show marked diversity in their electrophysiological properties and have been divided into four distinct subtypes. One question that arises from these observations is whether striatal TH-eGFP interneurons are distributed randomly, or obey some sort of organizational plan as has been shown to be the case with other striatal interneurons. An understanding of the striatal TH-eGFP interneuronal patterning is a vital step in understanding the role of these neurons in striatal functioning. Therefore, in the present set of studies the location of electrophysiologically identified striatal TH-eGFP interneurons was mapped. In addition, the distribution of TH-eGFP interneurons with respect to the striatal striosome-matrix compartmental organization was determined using µ-opioid receptor (MOR) immunofluorescence or intrinsic TH-eGFP fluorescence to delineate striosome and matrix compartments. Overall, the distribution of the different TH-eGFP interneuronal subtypes did not differ in dorsal versus ventral striatum. However, striatal TH-eGFP interneurons were found to be mostly in the matrix in the dorsal striatum whereas a significantly higher proportion of these neurons was located in MOR-enriched domains of the ventral striatum. Further, the majority of striatal TH-eGFP interneurons was found to be located within 100 µm of a striosome-matrix boundary. Taken together, the current results suggest that TH-eGFP interneurons obey different organizational principles in dorsal versus ventral striatum, and may play a role in communication between striatal striosome and matrix compartments.

Dopaminergic presynaptic modulation of nigral afferents: its role in the generation of recurrent bursting in substantia nigra pars reticulata neurons.

PREVIOUS WORK HAS SHOWN THE FUNCTIONS ASSOCIATED WITH ACTIVATION OF DOPAMINE PRESYNAPTIC RECEPTORS IN SOME SUBSTANTIA NIGRA PARS RETICULATA (SNR) AFFERENTS: (i) striatonigral terminals (direct pathway) posses presynaptic dopamine D(1)-class receptors whose action is to enhance inhibitory postsynaptic currents (IPSCs) and GABA transmission. (ii) Subthalamonigral terminals posses D(1)- and D(2)-class receptors where D(1)-class receptor activation enhances and D(2)-class receptor activation decreases excitatory postsynaptic currents. Here we report that pallidonigral afferents posses D(2)-class receptors (D(3) and D(4) types) that decrease inhibitory synaptic transmission via presynaptic modulation. No action of D(1)-class agonists was found on pallidonigral synapses. In contrast, administration of D(1)-receptor antagonists greatly decreased striatonigral IPSCs in the same preparation, suggesting that tonic dopamine levels help in maintaining the function of the striatonigral (direct) pathway. When both D(3) and D(4) type receptors were blocked, pallidonigral IPSCs increased in amplitude while striatonigral connections had no significant change, suggesting that tonic dopamine levels are repressing a powerful inhibition conveyed by pallidonigral synapses (a branch of the indirect pathway). We then blocked both D(1)- and D(2)-class receptors to acutely decrease direct pathway (striatonigral) and enhance indirect pathways (subthalamonigral and pallidonigral) synaptic force. The result was that most SNr projection neurons entered a recurrent bursting firing mode similar to that observed during Parkinsonism in both patients and animal models. These results raise the question as to whether the lack of dopamine in basal ganglia output nuclei is enough to generate some pathological signs of Parkinsonism.

Electrophysiological and morphological characteristics and synaptic connectivity of tyrosine hydroxylase-expressing neurons in adult mouse striatum.

Whole-cell recordings were obtained from tyrosine hydroxylase-expressing (TH(+)) neurons in striatal slices from bacterial artificial chromosome transgenic mice that synthesize enhanced green fluorescent protein (EGFP) selectively in neurons expressing TH transcriptional regulatory sequences. Stereological cell counting indicated that there were approximately 2700 EGFP-TH(+) neurons/striatum. Whole-cell recordings in striatal slices demonstrated that EGFP-TH(+) neurons comprise four electrophysiologically distinct neuron types whose electrophysiological properties have not been reported previously in striatum. EGFP-TH(+) neurons were identified in retrograde tracing studies as interneurons. Recordings from synaptically connected pairs of EGFP-TH(+) interneurons and spiny neurons showed that the interneurons elicited GABAergic IPSPs/IPSCs in spiny neurons powerful enough to significantly delay evoked spiking. EGFP-TH(+) interneurons responded to local or cortical stimulation with glutamatergic EPSPs. Local stimulation also elicited GABA(A) IPSPs, at least some of which arose from identified spiny neurons. Single-cell reverse transcription-PCR showed expression of VMAT1 in EGFP-TH(+) interneurons, consistent with previous suggestions that these interneurons may be dopaminergic as well as GABAergic. All four classes of interneurons were medium sized with modestly branching, varicose dendrites, and dense, highly varicose axon collateral fields. These data show for the first time that there exists in the normal rodent striatum a substantial population of TH(+)/GABAergic interneurons comprising four electrophysiologically distinct subtypes whose electrophysiological properties differ significantly from those of previously described striatal GABAergic interneurons. These interneurons are likely to play an important role in striatal function through fast GABAergic synaptic transmission in addition to, and independent of, their potential role in compensation for dopamine loss in experimental or idiopathic Parkinson's disease.

Analgesia preventiva en hembras Caninas sometidas a Ovariohisterectomía: comparación del efecto analgésico de Morfina y Tramadol asociados a Xilazina / Comparison of the Preventive Analgesic Effect Between Tramadol and Morphine Associated to Xylazine in Canine Ovaryhisterectomy

El objetivo del presente estudio fue comparar y evaluar el grado de analgesia postquirúrgica otorgado por Tramadol o morfina asociados a xilazina administrados por vía intramuscular (IM) en hembras caninas sometidas a ovariohisterectomía (OVH). Se utilizaron 24 animales adultos, sin distinción de raza y edad. Previo al procedimiento quirúrgico, los animales se dividieron en forma aleatoria conformado uno de los siguientes grupos: Grupo Control: 0,5 mg/kg de xilazina, Grupo Morfina: 0,5 mg/kg de xilazina + 0,4 mg/kg de morfina y Grupo Tramadol: 0,5 mg/kg de xilazina + 3 mg/kg de Tramadol. Las cirugías se desarrollaron de forma rutinaria sin presentarse anormalidades bajo anestesia general con isoflurano. La evaluación se inició 30 minutos postextubación durante 10 horas, a intervalos de 30 minutos, las primeras 6 horas y cada 1 hora por las siguientes 4 horas. El grado de algesia fue determinado mediante una escala de valoración numérica (EVN). Las diferencias entre tratamientos se evaluaron utilizando análisis de varianza de Kruskall Wallis y el método de comparación múltiple de Wilcoxon, considerando significativo un valor de P menor a 0,05. Los valores de algesia presentaron diferencias estadísticamente significativas (P<0,05) entre las tres, tres y media, cuatro y las siete horas de estudio entre los grupos control y Tramadol. A las seis, nueve y diez horas, las diferencias estadísticamente significativas (P<0,05) se dieron entre el grupo control y el grupo morfina y entre las cuatro horas treinta minutos, las cinco horas treinta minutos y las ocho horas, estas diferencias se dieron entre el grupo control y los grupos morfina y Tramadol. Del presente estudio se puede concluir que la administración preventiva de Tramadol o morfina asociados a xilazina otorgan buen efecto analgésico y que, en base a la respuesta algésica presentada en el periodo postoperatorio, ambos fármacos son eficaces y seguros para el control del dolor agudo postquirúrgico en hembras caninas sometidas a ovariohisterectomía.

The objective of the present study was to compare and evaluate the postoperative analgesic effects after the preventive administration of Tramadol and Morphine combined with Xylazine in canine ovarihysterectomy. Twenty four adult bitches without distinction of race and age were used. Animals were randomly assigned to three different groups receiving respectively: Control Group: 0.5 mg/kg Xilazine, Tramadol Group 0.5 mg/kg xilazine + 3 mg/kg Tramadol and Morphine Group: 0.5 mg/kg Xilazine + 0.4 mg/kg Morphine. Surgeries were carried out without complications under general anaesthesia under Isoflurane. Pain evaluations started 30 minutes after removing the endotracheal tube and carried out for 10 hours every thirty minutes for the first six hours and then every hour. Pain scores were determined using a numerical rating scale. Pain scores between different treatments were analyzed using Kruskall-Wallis non-parametric analysis of variance. A value of P<0.05 was considered to be statistically significant. Pain scores showed significant differences (P<0.05) between control and Tramadol groups at third, third and a half, fourth and seventh hour. Similarly at six, nine and ten hours of evaluation significant differences (P<0.05) between control and Morphine groups were found. Finally at four hour thirty minutes, the five hours thirty minutes and the eigth hour these significant differences (P<0.05) were between control and Morphine and Tramadol groups. It can be concluded that Tramadol and Morphine are effective and safe for the control of early post surgical pain in canine ovariohysterectomy.

Heterogeneity and diversity of striatal GABAergic interneurons.

The canonical view of striatal GABAergic interneurons has evolved over several decades of neuroanatomical/neurochemical and electrophysiological studies. From the anatomical studies, three distinct GABAergic interneuronal subtypes are generally recognized. The best-studied subtype expresses the calcium-binding protein, parvalbumin. The second best known interneuron type expresses a number of neuropeptides and enzymes, including neuropeptide Y, somatostatin, and nitric oxide synthase. The last GABAergic interneuron subtype expresses the calcium binding protein, calretinin. There is no overlap or co-localization of these three different sets of markers. The parvalbumin-immunoreactive GABAergic interneurons have been recorded in vitro and shown to exhibit a fast-spiking phenotype characterized by short duration action potentials with large and rapid spike AHPs. They often fire in a stuttering pattern of high frequency firing interrupted by periods of silence. They are capable of sustained firing rates of over 200 Hz. The NPY/SOM/NOS interneurons have been identified as PLTS cells, exhibiting very high input resistances, low threshold spike and prolonged plateau potentials in response to intracellular depolarization or excitatory synaptic stimulation. Thus far, no recordings from identified CR interneurons have been obtained. Recent advances in technological approaches, most notably the generation of several BAC transgenic mouse strains which express a fluorescent marker, enhanced green fluorescent protein, specifically and selectively only in neurons of a certain genetic makeup (e.g., parvalbumin-, neuropeptide Y-, or tyrosine hydroxylase-expressing neurons etc.) have led to the ability of electrophysiologists to visualize and patch specific neuron types in brain slices with epifluorescence illumination. This has led to a rapid expansion of the number of neurochemically and/or electrophysiologically identified interneuronal cell types in the striatum and elsewhere. This article will review the anatomy, neurochemistry, electrophysiology, synaptic connections, and function of the three "classic" striatal GABAergic interneurons as well as more recent data derived from in vitro recordings from BAC transgenic mice as well as recent in vivo data.

Diversity in long-term synaptic plasticity at inhibitory synapses of striatal spiny neurons.

Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term potentiation (LTP) at synapses among spiny neurons (intrinsic striatal circuitry); a postsynaptically dependent long-term depression (LTD) at synapses between spiny and pallidal neurons (indirect pathway); and a presynaptically dependent LTP at strionigral synapses (direct pathway). Interestingly, long-term synaptic plasticity differs at these synapses. The functional consequences of these long-term plasticity variations during learning of procedural memories are discussed.

Activation of the cholinergic system endows compositional properties to striatal cell assemblies.

Striatal cell assemblies are thought to encode network states related to associative learning, procedural memory, and the sequential organization of behavior. Cholinergic neurotransmission modulates memory processes in the striatum and other brain structures. This work asks if the activity of striatal microcircuits observed in living nervous tissue, with attributes similar to cell assemblies, exhibit some of the properties proposed to be necessary to compose memory traces. Accordingly, we used whole cell and calcium-imaging techniques to investigate the cholinergic modulation of striatal neuron pools that have been reported to exhibit several properties expected from cell assemblies such as synchronous states of activity and the alternation of this activity among different neuron pools. We analyzed the cholinergic modulation of the activity of neuron pools with multidimensional reduction techniques and vectorization of network dynamics. It was found that the activation of the cholinergic system enables striatal cell assemblies with properties that have been posited for recurrent neural artificial networks with memory storage capabilities. Graph theory techniques applied to striatal network states revealed sequences of vectors with a recursive dynamics similar to closed reverberating cycles. The cycles exhibited a modular architecture and a hierarchical organization. It is then concluded that, under certain conditions, the cholinergic system enables the striatal microcircuit with the ability to compose complex sequences of activity. Neuronal recurrent networks with the characteristics encountered in the present experiments are proposed to allow repeated sequences of activity to become memories and repeated memories to compose learned motor procedures.

Esofagectomia taanshiatal: informe historico de un csso / Transhyatal esophagectomy: Historical case

Se presenta un hombre de 57 años de edad con cáncer de esófago, localizado en tercio medio al que se realizó esofagectomía transhiatal sin toracotomía con esogastroplastia tubular ascendiendo la sustitución por el mediastino posterior, cuyo objetivo fue realizar la descripción del primer caso operado en el país por este método (1983), su evolución y resultados. Se presentó un paciente con disfagia de 3 meses de evolución y pérdida de 25 libras de peso; en su evolución postoperatoria se presentan complicaciones como neumotórax, derrame pleural y fístula esofágica las dos primeras tratadas con procedimientos quirúrgicos sencillos y la última con alimentación parenteral; cerró espontáneamente y egresó a los 31 días de operado. En conclusión, se presenta un caso histórico y anecdótico de un procedimiento aceptado internacionalmente y desarrollado en varios centros hospitalarios del país.

We present a 57 years old male patient with middle third esophagus carcinoma to whom we perform a transhiatal esopagectomy without toracothomy, utilizing a tubular ascending esophagogastroplasty substituting it with the posterior mediastinum. Main: To describe the first case operated in our country by this technique (1983), its evolution and results. Presentation: Patient with a three month lasting dysphagia, which has lost 12 Kg of weight, in his post surgical he had has had pneumothorax, pleural effusion and esophageal fistulae the first two treated with simple procedures and being discharged after 31 days post surgical. Conclusions: We make known a historical and anecdotic case treated with a procedure internationally accepted; already developed in various health care centers in our country.

Esofagectomía transhiatal: informe histórico de un caso / Transhyatal esophagectomy: historical case

Se presenta un hombre de 57 años de edad con cáncer de esófago, localizado en tercio medio al que se realizó esofagectomía transhiatal sin toracotomía con esogastroplastia tubular ascendiendo la sustitución por el mediastino posterior, cuyo objetivo fue realizar la descripción del primer caso operado en el país por este método (1983), su evolución y resultados. Se presentó un paciente con disfagia de 3 meses de evolución y pérdida de 25 libras de peso; en su evolución postoperatoria se presentan complicaciones como neumotórax, derrame pleural y fístula esofágica las dos primeras tratadas con procedimientos quirúrgicos sencillos y la última con alimentación parenteral; cerró espontáneamente y egresó a los 31 días de operado. En conclusión, se presenta un caso histórico y anecdótico de un procedimiento aceptado internacionalmente y desarrollado en varios centros hospitalarios del país(AU)

We present a 57 years old male patient with middle third esophagus carcinoma to whom we perform a transhiatal esopagectomy without toracothomy, utilizing a tubular ascending esophagogastroplasty substituting it with the posterior mediastinum. Main: To describe the first case operated in our country by this technique (1983), its evolution and results. Presentation: Patient with a three month lasting dysphagia, which has lost 12 Kg of weight, in his post surgical he had has had pneumothorax, pleural effusion and esophageal fistulae the first two treated with simple procedures and being discharged after 31 days post surgical. Conclusions: We make known a historical and anecdotic case treated with a procedure internationally accepted; already developed in various health care centers in our country(AU)

Bursting in substantia nigra pars reticulata neurons in vitro: possible relevance for Parkinson disease.

Projection neurons of the substantia nigra reticulata (SNr) convey basal ganglia (BG) processing to thalamocortical and brain stem circuits responsible for movement. Two models try to explain pathological BG performance during Parkinson disease (PD): the rate model, which posits an overexcitation of SNr neurons due to hyperactivity in the indirect pathway and hypoactivity of the direct pathway, and the oscillatory model, which explains PD as the product of pathological pattern generators disclosed by dopamine reduction. These models are, apparently, incompatible. We tested the predictions of the rate model by increasing the excitatory drive and reducing the inhibition on SNr neurons in vitro. This was done pharmacologically with bath application of glutamate agonist N-methyl-d-aspartate and GABA(A) receptor blockers, respectively. Both maneuvers induced bursting behavior in SNr neurons. Therefore synaptic changes forecasted by the rate model induce the electrical behavior predicted by the oscillatory model. In addition, we found evidence that Ca(V)3.2 Ca(2+) channels are a critical step in generating the bursting firing pattern in SNr neurons. Other ion channels involved are: hyperpolarization-activated cation channels, high-voltage-activated Ca(2+) channels, and Ca(2+)-activated K(+) channels. However, although these channels shape the temporal structure of bursting, only Ca(V)3.2 Ca(2+) channels are indispensable for the initiation of the bursting pattern.

Neuronal precursors within the adult rat subventricular zone differentiate into dopaminergic neurons after substantia nigra lesion and chromaffin cell transplant.

Neurogenesis in the adult mammalian brain continues in the subventricular zone (SVZ). Neuronal precursors from the SVZ migrate along the rostral migratory stream to replace olfactory bulb interneurons. After the destruction of the nigro-striatal pathway (SN-lesion), some SVZ precursors begin to express tyrosine hydroxylase (TH) and neuronal markers (NeuN). Grafting of chromaffin cells (CCs) into the denervated striatum increases the number of TH+ cells (SVZ TH+ cells; Arias-Carrión et al., 2004). This study examines the functional properties of these newly differentiating TH+ cells. Under whole-cell patch-clamp, most SVZ cells recorded from lesioned and grafted animals (either TH+ or TH-) were non-excitable. Nevertheless, a small percentage of SVZ TH+ cells had the electrophysiologic phenotype of mature dopaminergic neurons and showed spontaneous postsynaptic potentials. Dopamine (DA) release was measured in SVZ and striatum from both control and SN-lesioned rats. As expected, 12 weeks after SN lesion, DA release decreased drastically. Nevertheless, 8 weeks after CCs graft, release from the SVZ of SN-lesioned rats recovered, and even surpassed that from control SVZ, suggesting that newly formed SVZ TH+ cells release DA. This study shows for the first time that in response to SN-lesions and CC grafts neural precursors within the SVZ change their developmental program, by not only expressing TH, but more importantly by acquiring excitable properties of mature dopaminergic neurons. Additionally, the release of DA in a Ca(2+)-dependent manner and the attraction of synaptic afferents from neighboring neuronal networks gives further significance to the overall findings, whose potential importance is discussed.