Functional correlation between cerebellum and basal ganglia: A parkinsonism model.

INTRODUCTION: The cerebellar response has been studied for years with different models of alteration of other brain structures to understand its complex functioning and its relationship with the rest of the body. Studies in patients with Parkinson's disease (PD) showed that the cerebellar function is modified by deficit of the basal ganglia; which supports the hypothesis that both structures are related anatomically and functionally. METHODS: In our study, the ventrolateral striatum (VLS) of the basal ganglia was altered by an electrolytic lesion, in order to produce a similar jaw frequency of jaw tremor movements presented in parkinsonism, thereafter we analyzed the effect of the lesion on the expression of multiunit activity (MUA) of the cerebellum. RESULTS: We found cerebellar activation during mandibular movements and increment during oral jaw tremor movements. In addition, the amplitude of baseline MUA registered in animals with alteration of the VLS decreased with respect to the intact group. CONCLUSIONS: Accordingly, we conclude that cerebellar changes in MUA may be due to a decrease in the cerebellar inflectional or as a possible compensatory function between cerebellum and basal ganglia.

Nature and nurture of sexual partner preference: Teachings from prenatal administration of acetaminophen in male rats.

The organizational-activational hypothesis indicates that activation of adult sexual behavior in males depends on organization of the masculine brain during the perinatal sensitive period. In the medial preoptic area such masculinization depends on a neuroendocrine cascade that includes exposure to testosterone, aromatization to estradiol, activation of estrogen receptors, synthesis of cyclooxygenase (COX), increase of prostaglandins, release of glutamate, and activation of AMPA receptors that result in the formation of more dendritic spines. Thus, in the present study we assessed the sexual partner preference (SPP) of adult male rats prenatally treated with acetaminophen (APAP), an analgesic/antipyretic drug that inhibits COX-2 and is commonly used and prescribed during pregnancy. Female rats received either saline (2 ml/kg s.c.) or APAP (50 mg/kg s.c.) every 12 h, during days 16-20 of pregnancy. At postnatal day PD60 half of the male offspring were exposed to sexual experience with receptive females during 5 trials, and the other half remained sexually naïve. At PD90 all them were tested for SPP with one sexually receptive female and one stud male. The results indicated that only APAP-naïve males failed to display SPP. However, APAP-experienced males displayed SPP for females. We discuss the effects of prenatal APAP in the disruption of unconditioned responses towards females (nature mechanisms), and the effects of sexual experience (nurture mechanisms) in the development of conditioned heterosexual preference.

Olfactory conditioned same-sex partner preference in female rats: Role of ovarian hormones.

The dopamine D2-type receptor agonist quinpirole (QNP) facilitates the development of conditioned same-sex partner preference in males during cohabitation, but not in ovariectomized (OVX) females, primed with estradiol benzoate (EB) and progesterone (P). Herein we tested the effects of QNP on OVX, EB-only primed females. Females received a systemic injection (every four days) of either saline (Saline-conditioned) or QNP (QNP-conditioned) and then cohabited for 24h with lemon-scented stimulus females (CS+), during three trials. In test 1 (female-female) preference was QNP-free, and females chose between the CS+ female and a novel female. In test 2 (male-female) they chose between the CS+ female and a sexually experienced male. In test 1 Saline-conditioned females displayed more hops & darts towards the novel female, but QNP-conditioned females displayed more sexual solicitations towards the CS+ female. In test 2 Saline-conditioned females displayed a clear preference for the male, whereas QNP-conditioned females displayed what we considered a bisexual preference. We discuss the effect of dopamine and ovarian hormones on the development of olfactory conditioned same-sex preference in females.

Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats.

UNLABELLED: Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland. AIMS: The present study was designed to describe the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia. MATERIAL AND METHODS: Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and also with those treated with testosterone, or the combination of prolactin + testosterone. RESULTS: Rats treated with prolactin, testosterone or prolactin + testosterone expressed precancerous histological abnormalities in the dorsolateral and ventral portions of the prostate as early as in 4 weeks of treatment, but in all cases the malignancy increased after 12 or 24 weeks of treatment. CONCLUSION: Our study confirms that chronic hyperprolactinemia is a cause of prostate precancerous pathologies.

Beyond the basal ganglia: cFOS expression in the cerebellum in response to acute and chronic dopaminergic alterations.

The suggestion of an anatomical and functional relationship between the basal ganglia and cerebellum is recent. Traditionally, these structures were considered as neuronal circuits working separately to organize and control goal-directed movements and cognitive functions. However, several studies in rodents and primates have described an anatomical interaction between cortico-basal and cortico-cerebellar networks. Most importantly, functional changes have been observed in one of these circuits when altering the other one. In this context, we aimed to accomplish an extensive description of cerebellar activation patterns using cFOS expression (cFOS-IR) after acute and chronic manipulation of dopaminergic activity. In the acute study, substantia nigra pars compacta (SNc) activity was stimulated or suppressed by intra cerebral administration of picrotoxin or lidocaine, respectively. In addition, we analyzed cerebellar activity after the induction of a parkinsonism model, the tremulous jaw movements. In this model, tremulous jaw movements were induced in male rats by IP chronic administration of the dopamine antagonist haloperidol (1.5mg/kg). Acute stimulation of SNc by picrotoxin increased cFOS-IR in the vermis and cerebellar hemispheres. However, lidocaine did not produce an effect. After 14days of haloperidol treatment, the vermis and cerebellar hemispheres showed an opposite regulation of cFOS expression. Chronic dopaminergic antagonism lessened cFOS expression in the vermis but up-regulated such expression in the cerebellar hemisphere. Overall, the present data indicate a very close functional relationship between the basal ganglia and the cerebellum and they may allow a better understanding of disorders in which there are dopamine alterations.

Inhibition of endoplasmic reticulum Ca²âº ATPase in preBötzinger complex of neonatal rat does not affect respiratory rhythm generation.

PreBötzinger complex (preBötC) neurons in the brainstem underlie respiratory rhythm generation in vitro. As a result of network interactions, preBötC neurons burst synchronously to produce rhythmic premotor inspiratory activity. Each inspiratory neuron has a characteristic 10-20 mV, 0.3-0.8 s synchronous depolarization known as the inspiratory drive potential or inspiratory envelope, topped by action potentials (APs). Mechanisms involving Ca(2+) fluxes have been proposed to underlie the initiation of the inspiratory drive potential. An important source of intracellular Ca(2+) is the endoplasmic reticulum (ER) in which active Ca(2+) sequestration is mediated by a class of transporters termed sarco/endoplasmic reticulum Ca(2+) ATPases (SERCAs). We aim to test the hypothesis that disruption of Ca(2+) sequestration into the ER affects respiratory rhythm generation. We examined the effect of inhibiting SERCA on respiratory rhythm generation in an in vitro slice preparation. Bath application of the potent SERCA inhibitors thapsigargin or cyclopiazonic acid (CPA) for up to 90 min did not significantly affect the period or amplitude of respiratory-related motor output or integral and duration of inspiratory drive in preBötC neurons. We promoted the depletion of intracellular Ca(2+) stores by a transient bath application of 30 mM K(+) (high K(+)) in the continuous presence of thapsigargin or CPA. After washing out the high K(+), respiratory rhythm period and amplitude returned to baseline values. These results show that after inhibition of SERCA and depletion of intracellular Ca(2+) stores, respiratory rhythm remains substantially the same, suggesting that this source of Ca(2+) does not significantly contribute to rhythm generation in the preBötC in vitro.

Amino acid tissue levels and GABAA receptor binding in the developing rat cerebellum following status epilepticus.

Incidence of status epilepticus (SE) is higher in children than in adults and SE can be induced in developing rats. The cerebellum can be affected after SE; however, consequences of cerebellar amino acid transmission have been poorly studied. The goal of this study was to determine amino acid tissue concentration and GABA(A) receptor binding in the immature rat cerebellum after an episode of SE. Thirteen-day-old (P13) rat pups received intraperitoneal injections of lithium chloride (3 mEq/kg). Twenty hours later, on P14, SE was induced by subcutaneous injection of pilocarpine hydrochloride (60 mg/kg). Control animals were given an equal volume of saline subcutaneously. Animals were killed 24h after SE induction, the cerebellum was quickly removed, and the vermis and hemispheres were rapidly dissected out on ice. Amino acid tissue concentrations in the vermis and hemispheres were evaluated by HPLC and fluorescent detection. GABA(A) receptor binding in the medial vermis was analyzed by in vitro autoradiography. SE increased the tissue levels of the inhibitory amino acids taurine (80%) and alanine (91%), as well as glutamine (168%) in the cerebellar hemisphere; no changes were observed in the vermis. SE did not modify GABA(A) receptor binding in any cerebellar lobule from the vermis. Our data demonstrate that SE produces region-specific changes in amino acid concentrations in the developing cerebellum.

Neuroendocrine control of urine-marking behavior in male rats.

Sexually experienced Wistar male rats were used to investigate (a) urine voiding in the presence of nearby estrous females and the control of such voiding by (b) steroid hormones and (c) peripheral nerves supplying the genitourinary system. The first experiment showed that males always have a low rate of urine voiding that is significantly increased when a receptive female is around. Thus, it is suggested that an airborne scent from the female stimulates the olfactory system of males, triggering urine emission to transmit sex-related messages, i.e., male rats display the well-known urine-marking behavior of mammals. The number of urine marks and sniffing to females decreased after castration, and were restored after exogenous treatment with testosterone or estradiol. The proposed hypothesis is that airborne scents from the female activate the aromatization process in nuclei of the olfactory pathway of the male, evoking a cascade of neuronal responses that finish in urine marking. Peripheral nerves supplying the genitourinary system are the viscerocutaneous branch of the pelvic nerve (Vc) and the hypogastric (Hg). Data showed that both nerves are important for the central control of urine storage and voiding. Transection of Vc almost blocked urine marking, while Hg lesion increased the number of marks. Thus, it is discussed that Vc is the most important nerve in charge of voiding the bladder, and that Hg is important for continence.

Fertility ratio in male rats: effects after denervation of two pelvic floor muscles.

Fertility ratio is defined here as the proportion of females that a male can impregnate after a constant period of in-polygyny living. This ratio was investigated in male rats after denervation of two pelvic floor muscles, the pubococcygeus and iliococcygeus. Denervation was carried out by transecting the somatomotor branch of the pelvic nerve. The lesion did not modify the sexual behavior of males or their overall fertility, but decreased the weight of the ejaculated seminal plug. Consequently, the number of days living in cohabitation to induce pregnancy was increased in lesioned males (approximately 13 days) compared with intact and sham animals (approximately 5 days). These results showed that the fertility ratio was optimal when intact/sham males cohabited with females for two consecutive estrous cycles, but that lesioned males needed up to four cycles to induce most pregnancies. Two hypotheses are raised by our results. The first is that pelvic floor denervation decreases the forceful tension required to expel the semen from the prostatic urethra to the vagina, then an incomplete seminal plug is expelled. The second is that denervation cut afferent fibers that reflexively promote the continence of the semen deposited in the prostatic urethra during seminal emission, allowing some to leak out before ejaculation. The latter hypothesis can also explain the recovery of the fertility ratio in lesioned males. It could be a compensatory mechanism mediated by the pudendal nerve supply to the coccygeus muscle, the other pelvic floor muscle.

Regulation of noncontact erection in rats by gonadal steroids.

Male rats exhibit erections in the presence of inaccessible estrous females, and we investigated which gonadal steroids regulate these noncontact erections (NCEs). Sexually experienced Wistar males (n >/= 8/group) were tested for NCE four times (every 3 days) before castration, after castration, and after receiving subcutaneous implants of 10-mm Silastic capsules that were empty or filled with crystalline testosterone propionate (TP), dihydrotestosterone (DHT), estradiol benzoate (EB), or DHT + EB (10 mm each). Before castration, males responded with NCE in approximately 50% of tests. No males had NCEs after castration, beginning 3 days after surgery. Also, no males responded after treatment with EB or empty capsules. After receiving implants of TP, DHT, or DHT + EB, 50% of males had NCEs, beginning with the first test 3 days after treatment. On every measure of NCE, males treated with DHT or DHT + EB were indistinguishable from each other and from TP-treated males. Among the sexual responses of male rats, NCE appears to be more sensitive than other behaviors to changes in gonadal condition. In its profile of response to gonadal steroids (testosterone+, dihydrotestosterone+, estradiol-), NCE is similar to reflexive erection, for which spinal systems are sufficient, and unlike copulation (T+, DHT-, E+), which depends on discrete areas of the brain. We nonetheless conclude that NCE depends on androgen-sensitive systems in the brain, but androgen-sensitive neurons in the lumbosacral spinal cord may also play a role.

Peripheral nerves mediating penile erection in the rat.

We examined the effects in male rats of bilateral transection of two nerves previously implicated in erectile function, the viscerocutaneous branch of the pelvic nerve (Vc) and the hypogastric nerve (HgN). In Experiment 1 (conducted in Storrs), males underwent simultaneous or successive section of Vc and HgN and were tested for copulation, reflexive erection, and noncontact erection (NCE), i.e. in response to remote cues from estrous females. NCE is considered to be analogous to 'psychogenic' erection in humans, for which the HgN has been ascribed a significant role. In all three types of test, males had a moderate to severe deficit in erectile function after Vc transection. Section of HgN alone had no apparent pro- or anti-erectile effect in any context, nor did it affect the decrement resulting from Vc surgery. Regardless of treatment, all groups retained some erectile potential in each type of test. The loss of bladder function after Vc surgery and of seminal plug deposition after HgN section gave evidence that the targeted nerves were in fact severed. In Experiment 2 (conducted in Xalapa), males were tested only for NCE, but (a) they were tested every 3 days beginning 3 days after each surgery, (b) the interval between the two surgeries was more than 2 weeks, rather than 1 week as in Experiment 1, to allow more time for recovery from general effects of surgery and for hypothetical plasticity of neural function. In the first test after the first surgery, all groups had a modest reduction in the proportion of males displaying NCE, relative to sham-operated males. However, this deficit did not extend to measures of NCE latency or number, and was absent after the second test. After the second surgery, when all males except those with sham operations had both nerves cut, none of the groups exhibited a significant deficit in NCE, and all groups had at least one test in which at least half the males responded. Thus, (a) HgN section did not significantly impair NCE, reflexive erection, or copulation; (b) Vc section impaired, but did not eliminate, erection in all three contexts, but even those effects may be transient; and (c) transection of both nerves, simultaneously or successively, did not cause a greater impairment in erection than did cutting just the Vc. We infer that the HgN may have no pro-erectile role in erection in rats, even in a model analogous to psychogenic erection. The Vc is probably the most important nerve mediating pro-erectile function in NCE, as in reflexive erection and copulation, but this nerve may not be essential for erection in rats in any context, at least in some males.