No description available.

Schizophrenia is a neurological disorder found in approximately 1% of the population. It is estimated that as many as 88% of individuals diagnosed which schizophrenia smoke tobacco, a rate which is greatly increased compared to the general population. While increased use of nicotine-containing products such as cigarettes may be detrimental to the long-term health of individuals with schizophrenia, it has been hypothesized that nicotine use is a form of self-medication for these individuals who suffer from serious neurological and psychological symptoms such as hallucinations, delusions, anhedonia, and cognitive impairments. Understanding the biomolecular mechanisms which result in a higher propensity for smoking may lead to an overall better understanding of the disease and new treatment options. This study investigated the effects of nicotine in an epigenetic transmission model of schizophrenia. Rats were treated neonatally with the dopamine D2 agonist quinpirole or saline from P1 to P21 and then raised into adulthood. This paradigm has been previously shown to produce rats with symptoms similar to schizophrenia, including an enhanced response to nicotine. These neonatally treated rats were then bred to produce pups which were not neonatally treated to investigate whether schizophrenia-like symptoms would be transmitted to the untreated offspring of the quinpirole treated parents in the context of nicotine administration, similar to that of their parents. To examine the effects of nicotine, the rats that were the offspring of animals that were neonatally treated quinpirole were behaviorally tested on either a behavioral sensitization or conditioned place preference (CPP) paradigm, and animals received either nicotine or saline. Following behavioral testing, brain tissue was collected, and an ELISA for brain-derived neurotrophic factor (BDNF) was performed. Results revealed that these offspring demonstrated a heightened behavioral response to nicotine as well as increased expression of BDNF following nicotine administration if at least one parent rat was neonatally treated with quinpirole. This indicates that there may be epigenetic information passed from parents neonatally treated with quinpirole to the offspring.

Two interesting properties of the distribution of spatially selective attention have been noted in the behavioral and electrophysiological literature. First, there is a graded field of attention that expands from the center of the attended area. Second, the size of the attended area can be adjusted to be either larger or smaller in order to match the demands of the current task. Five event-related potential (ERP) studies are presented that extend these findings in several important ways; 1) The time frame of these two distribution properties is different. Results are consistent with a two stage model of spatial attention in which visual processing is initially enhanced for all stimuli presented near the center of the attended area as indexed by the amplitude of the first negative peak in the waveform (N1). Subsequently, the effects of narrowing or expanding the attentional field to the relevant size affects visual processing as indexed by the amplitude of the second negative peak (N2). 2) Object boundaries had limited impact on either the spread of the initial gradient of spatial selection or the scale of attention. 3) When selecting visual stimuli for attentive processing based on features such as color and size there is also a gradient of facilitation, but the impact of this graded selection on visual processing is not observed until later in processing, and is indexed by the amplitude of the selection negativity (SN). Furthermore, similar to the lack of interaction between object boundaries and the range of cued locations, the gradients of feature-based selection are not affected by the range of cued features.

Chronic pain is one of the most prevalent medical conditions in the US. Besides physical symptoms, it has a profound impact on mental health and quality of life. The physiological mechanisms underlying chronic pain are complex; thus, treatments are limited. Opioid analgesics are one of the most commonly prescribed medications for the management of chronic pain; however, a major pitfall of the use of opioids is their addictive potential. Here we examine, in a mouse model, how chronic pain influences opioid addiction, with the hypothesis that chronic pain potentiates addiction due to the dual rewarding effects of opioids—euphoria and analgesia. We tested this using conditioned place preference (CPP), and find that this is not the case, as acquisition of a drug memory was attenuated under a chronic pain context. We also observe that chronic pain may facilitate extinction of the drug memory, suggesting that the mechanism of addiction under a chronic pain context is more complex than previously assumed. This complex behavioral phenotype is possibly a reflection of the underlying neural mechanisms involving multiple brain regions. In order to start understanding this mechanism, we mapped the expression of immediate early genes brain wide to identify key brain regions involved in both chronic pain and addiction. The prefrontal cortex (PFC) is one major brain region known to directly modulate circuits involved in both pain and drug addiction. However, the PFC consists of a myriad of cell types that project to distinct downstream targets, whose roles in specific behaviors are still largely unknown. A recent study classified the different subtypes of neurons in the PFC using single cell RNA sequencing (scRNA-seq), which identified a layer 5 pyramidal neuron (Pou3f1+) that is involved in pain and opioid taking. Using chemogenetic techniques, we manipulated the activity of Pou3f1+ neurons to test their response under pain and opioid use. These neurons appear to bi-directionally regulate pain perception, as activation increases mechanical sensitivity measured using von Frey filaments, and inhibition diminishes sensitivity. On the other hand, opioid administration under a chronic pain state potently activated Pou3f1+ neurons, as determined by cfos mRNA expression. These findings indicate potential interactions between the neural processing of chronic pain and opioid addiction, opening up the possibility of exploring common brain regions, and ultimately discrete cell types that can be therapeutically targeted to alleviate pain without the risk of addiction. / 2025-01-27T00:00:00Z

The genital chamber is a structure that is important for mating, egg progression, and fertilization in female crickets. The activity and efferent control of the genital chamber and its retractor, muscle 2, are characterized using electrophysiology, intracellular dye injections, and immunohistochemistry in a dissected preparation of female Acheta domesticus. Rhythmic activity in nerves 7v and 8v underlies movements of the genital chamber, and rhythmically-active motor neurons in the terminal abdominal ganglion supply the genital chamber and muscle 2. Some of these motor neurons were identified on the basis of intracellularly-recorded activity, axonal projections, target muscle, and/or central anatomy. Rhythmic 8v motor neurons in the terminal abdominal ganglion have two morphological types; one type shows diffuse or stringy projections and the physiological characteristic of soma spikes. Rhythmic motor neurons do not show properties such as plateau potentials, which are consistent with endogenous oscillation; it is suggested that they receive rhythmic synaptic drive. A bilateral pair of identified rhythmic motor neurons in the 8th segment contains serotonin and projects to the genital chamber. Serotonergic fibers on the genital chamber are the endings of this pair of neurons exclusively. Other serotonergic neurons in the terminal ganglion project to motor and integrative areas, and serotonin is differentially localized in sensory projection areas of the 7th and 8th versus the 9th and 10th neuromeres. These results suggest that serotonin could be involved in the modulation of mechanosensory information, as well as modulating pattern-generating circuitry in the terminal ganglion. This system presents a model for investigating the role of serotonin in neuromuscular transmission, and in the integration of neural circuits for behavior.

No description available.

Studies on the evolution of the mammalian brain suggest that changes in subcortical structures include the division of the once continuous bed nucleus of the stria terminalis (BST) and medial amygdaloid nucleus (MA). Within each of these two areas is a group of vasopressin (AVP) cells, which together form the sexually dimorphic AVP system. Studies carried out for this thesis answered questions on the development and morphology of this system, with special reference to the evolutionary relationship between its two AVP cell groups. The first study tested whether, when placed in the same environment, developing AVP cells of the BST and MA can innervate similar targets. AVP cells in BST or MA fetal grafts showed similar fiber outgrowth into the lateral septum of adult AVP-deficient Brattleboro rats, which is inconsistent with the paucity of AVP projections from the MA to the lateral septum of non-deficient rats. This inconsistency suggests that developing AVP cells of the BST and MA can respond to similar environmental cues. The second study tested whether the AVP cells of the BST and MA have similar birthdates. Combining AVP and bromo-5-deoxy-2-uridine (BrdU) immunocytochemistry suggests that most AVP cells within the BST and MA are born around embryonic days (E) 12-E13, which is surprising, since this and previous studies suggest that most cells within the same divisions of the BST and MA are born around E14-16. No differences were found between birthdates of AVP cells in the BST and MA. However, there were differences between males and females. Females had proportionally more AVP cells colocalized with BrdU on E13. The third study tested whether projections of AVP cells in the BST and MA are similar. Anterograde tracing suggests that AVP cells of the BST and MA contribute in different proportions to the innervation of forebrain areas that contain sexually dimorphic AVP fibers. Retrograde tracing combined with AVP immunocytochemistry suggests that more AVP cells in the BST project to the lateral septum than AVP cells in the MA. These studies raise questions about the structural and functional development of the mammalian brain. Using the sexually dimorphic AVP system as an example for other systems, some of these questions are discussed in the final chapter.

To see if the vasopressinergic system, implicated in maternal behavior, changes during parenthood in different directions in males and females, I examined the pattern of vasopressin immunoreactivity in prairie voles in which both mother and father care for young and meadow voles in which only the mother cares for young. For both species, I compared the densities of vasopressin immunoreactive (AVP-ir) fibers in males and females that were either sexually naive or in parental state. In both species, AVP-ir fiber densities in the lateral septum (LS), and the lateral habenular nucleus (LHN) were higher in males than in females regardless of their parental state. AVP-ir fiber density in the LS and the LHN was reduced in parental prairie-vole males, while no differences were found in females. The AVP-ir in the LS of parental meadow-vole males and females did not show changes, while the fiber density in their LHN was increased. To see if AVP immunoreactivity in male prairie voles changes before or after the birth of pups, I compared AVP-ir fiber density among males and females that were either housed separately or housed together until after mating (3-P), during early gestation (13-P) or late gestation (21-P), or after the birth of pups (26-P). Under all these conditions, AVP-ir fibers in the LS and the LHN were much denser in males than in females. In males, the lowest density of AVP-ir in the LS and the LHN was found in 3-P males. An intermediate density was found in 13-P and 26-P males. An equally high density was found in sexually naive (0-M) and in 21-P males. In females, no changes in AVP immunoreactivity were found. The decrease in AVP-ir fibers of 3-P males occurred only in presence of a female. Changes in AVP immunoreactivity of male prairie voles could be related either to sexual activity which takes place after the first 3 days of cohabitation and again around pups' birth, behavioral changes associated with pair bonding, or induction of paternal behavior.

The purpose was to assess the specificity of muscular fatigue and changes in the stretch-evoked forces and integrated surface electromyographic (EMG) activity of the vastus lateralis and biceps femoris muscles in 12 endurance and 12 power athletes. On each of four separate days, fatigue was induced with 49 repetitions of isometric, shortening, and lengthening knee extension and with 1-min continuous vertical jumping. Before and after fatigue, testing included 5-s isometric knee extension with a superimposed stretch, shortening, and lengthening knee extension. Endurance and power athletes produced significantly greater lengthening and stretch forces compared to isometric and shortening forces. Within each group, lengthening and stretch forces were not different. Isometric force was significantly greater than shortening force in power but not in endurance athletes. Power athletes averaged 57.4% stronger than endurance athletes for the three measures of knee extension strength. Power athletes produced significantly more integrated EMG during isometric, shortening, and lengthening knee extension than endurance athletes, but there were no between-group differences in the integrated EMG of the biceps femoris. Endurance athletes showed significantly less stretch-evoked force potentiation (10.4 N x 10) than power athletes (14.4 N x 10). Expressed as a percentage of isometric force, the superimposed stretch increased force production by 20% in endurance and 15% in power athletes. The integrated EMG due to the stretch increased by 37.6 and 21.7 $\mu$V$\cdot$s or 23% and 15% in power and in endurance athletes. Based on the stretch-evoked force-to-EMG ratios, endurance athletes used approximately twice as much neural drive to potentiate the same amount of force as power athletes. Endurance athletes showed significantly less force fatigue ($\sim$7%) than power athletes (26%) for isometric, shortening, and lengthening knee extension exercise. Muscular fatigue was the greatest with lengthening exercise in power but not in endurance athletes, 5 of whom increased lengthening force by the 49th repetition. Fatigue in the endurance athletes was the greatest after the 1-min vertical jumping protocol (-6.4%). The average decline in the integrated EMG of the vastus lateralis was 17% and 22% in endurance and power athletes. Stretch-evoked force did not change with fatigue, while EMG potentiation significantly declined after the four fatigue protocols in both groups. For the endurance and power athletes, there was no indication for specificity of force or EMG fatigue. Thus, the current data suggest that in two groups of athletes, muscular fatigue was general in terms of force loss and EMG activity assessed by three test modes and four fatigue protocols.

In three experiments, rats received a single simultaneous pairing of a 4-s conditioned stimulus (CS) and a 4-s grid shock unconditioned stimulus (US) in which the CS and US began together. The CS was either an element (tone, light, or noise) or a compound composed of two elements (tone + light or tone + noise). In a fourth experiment, rats received a single backward pairing of a 4-s CS and a 4-s grid shock US in which the CS began at US offset. The CS was either a tone or a tone + light compound. Freezing and the suppression of licking elicited by the CS provided evidence for excitatory 1-trial simultaneous and 1-trial backward conditioning to the element and to the compound CSs. There was no evidence of greater conditioning to the compound CSs as compared to either of their constituent elements. An analysis of a videotaped record of the behavior of the rats in Experiment 2 revealed somewhat less freezing to the light than to the tone, but no evidence of a defensive behavior unique to light. Thus the defensive behavior to CSs associated with aversive USs is freezing, regardless of CS modality.