Amygdalar Corticotropin-Releasing Factor Signaling Is Required for Later-Life Behavioral Dysfunction Following Neonatal Pain.

Neonatal pain such as that experienced by infants in the neonatal intensive care unit is known to produce later-life dysfunction including heightened pain sensitivity and anxiety, although the mechanisms remain unclear. Both chronic pain and stress in adult organisms are known to influence the corticotropin-releasing factor (CRF) system in the Central Nucleus of the Amygdala, making this system a likely candidate for changes following neonatal trauma. To examine this, neonatal rats were subjected to daily pain, non-painful handling or left undisturbed for the first week of life.

Maternal separation with neonatal pain influences later-life fear conditioning and somatosenation in male and female rats.

Early life adversity, including that which occurs in a medical setting, has been increasingly shown to have lasting consequences on both physical and mental health. In order to understand the lasting effects of early-life adversity, such as that might occur in the neonatal intensive care unit (NICU), several rodent models have been developed including maternal separation, neonatal handling, and repeated needle prick pain. However, in the clinical scenario, these stressors are often combined.

The Effects of Acute Neonatal Pain on Expression of Corticotropin-Releasing Hormone and Juvenile Anxiety in a Rodent Model.

Premature infants in the neonatal intensive care unit (NICU) may be subjected to numerous painful procedures without analgesics. One necessary, though acutely painful, procedure is the use of heel lances to monitor blood composition. The current study examined the acute effects of neonatal pain on maternal behavior as well as amygdalar and hypothalamic activation, and the long-term effects of neonatal pain on later-life anxiety-like behavior, using a rodent model.

Inflammatory neonatal pain disrupts maternal behavior and subsequent fear conditioning in a rodent model.

Infants spending extended time in the neonatal intensive care unit are at greater risk of developing a variety of mental health problems later in life, possibly due to exposure to painful/stressful events. We used a rodent model of inflammatory neonatal pain to explore effects on fear conditioning, somatosensory function and maternal behavior. Hindpaw injections of 2% λ-carrageenan on postnatal days 1 and 4 produced an attenuation in conditioned freezing during the postweaning period, similar to our previous work with acute pain, but did not cause lasting impacts on contextual freezing nor somatosensory function.

Neonatal pain and stress disrupts later-life pavlovian fear conditioning and sensory function in rats: Evidence for a two-hit model.

Early life trauma has been linked to increased risks for anxiety, depression, and chronic pain. We used rodent models of acute and inflammatory neonatal pain to explore effects on fear conditioning and somatosensory function. Hindpaw needle pricks or handling on postnatal days (PNDs) 1-7 caused lasting impacts on affective and somatosensory function when assessed at later ages, PNDs 24 (postweaning), 45 (adolescence), or 66 (adulthood).

FAAH inhibitor OL-135 disrupts contextual, but not auditory, fear conditioning in rats.

Anxiety disorders are among the most prevalent psychological disorders, have significant negative impacts on quality of life and the healthcare system, and yet effective treatments remain elusive. Manipulating the endocannabinoid system has demonstrated potential for treating anxiety, although the side effects of direct manipulations of cannabinoid receptors keeps them from widespread clinical use. Disrupting the degradation enzyme fatty acid amide hydrolase (FAAH) enhances endogenous signaling and may produce similar efficacy without the side effects.

Limbic system development underlies the emergence of classical fear conditioning during the third and fourth weeks of life in the rat.

Classical fear conditioning creates an association between an aversive stimulus and a neutral stimulus. Although the requisite neural circuitry is well understood in mature organisms, the development of these circuits is less well studied. The current experiments examine the ontogeny of fear conditioning and relate it to neuronal activation assessed through immediate early gene (IEG) expression in the amygdala, hippocampus, perirhinal cortex, and hypothalamus of periweanling rats.

K-12 Neuroscience Education Outreach Program: Interactive Activities for Educating Students about Neuroscience.

The University of New England's Center for Excellence in the Neurosciences has developed a successful and growing K-12 outreach program that incorporates undergraduate and graduate/professional students. The program has several goals, including raising awareness about fundamental issues in neuroscience, supplementing science education in area schools and enhancing undergraduate and graduate/professional students' academic knowledge and skill set. The outreach curriculum is centered on core neuroscience themes including: Brain Safety, Neuroanatomy, Drugs of Abuse and Addiction, Neurological and Psychiatric Disorders, and Cognition and Brain Function.

Contextual and auditory fear conditioning continue to emerge during the periweaning period in rats.

Anxiety disorders often emerge during childhood. Rodent models using classical fear conditioning have shown that different types of fear depend upon different neural structures and may emerge at different stages of development. For example, some work has suggested that contextual fear conditioning generally emerges later in development (postnatal day 23-24) than explicitly cued fear conditioning (postnatal day 15-17) in rats.

Developing and validating trace fear conditioning protocols in C57BL/6 mice.

Background: Classical fear conditioning is commonly used to study the biology of fear, anxiety and memory. Previous research demonstrated that delay conditioning requires a neural circuit involving the amygdala, but not usually the hippocampus. Trace and contextual fear conditioning require the amygdala and hippocampus.

Evidence for hippocampus-dependent contextual learning at postnatal day 17 in the rat.

Long-term memory for fear of an environment (contextual fear conditioning) emerges later in development (postnatal day; PD 23) than long-term memory for fear of discrete stimuli (PD 17). As contextual, but not explicit cue, fear conditioning relies on the hippocampus; this has been interpreted as evidence that the hippocampus is not fully developed until PD 23. Alternatively, the hippocampus may be functional prior to PD 23, but unable to cooperate with the amygdala for fearful learning.

Role of corticosterone in trace and delay conditioned fear-potentiated startle in rats.

Emotional events often lead to particularly strong memory formation. Corticosterone, the final product of hypothalamic-pituitary-adrenal (HPA)-axis activation, has been suggested to play a critical role in this effect. Although a great deal of work has implicated the amygdala as a necessary structure for the effects of corticosterone, other studies have suggested a critical role for the hippocampus in determining the involvement of corticosterone.

Neonatal binge alcohol exposure produces dose dependent deficits in interstimulus interval discrimination eyeblink conditioning in juvenile rats.

Alcohol consumption in neonatal rats produces cerebellar damage and is widely used to model 3rd-trimester human fetal alcohol exposure. Neonatal "binge-like" exposure to high doses of alcohol (5 g/kg/day or more) impairs acquisition of eyeblink classical conditioning (EBC), a cerebellar-dependent Pavlovian motor learning task. We have recently found impairments in interstimulus interval (ISI) discrimination--a complex task variant of EBC--in adult rats following postnatal day (PD) 4-9 alcohol exposure at doses of 3, 4, and 5 g/kg/day.

Hippocampal activity, but not plasticity, is required for early consolidation of fear conditioning with a short trace interval.

The dorsal hippocampus is required for explicit cue fear conditioning only when a temporal gap is inserted between conditioned stimulus (CS) termination and unconditioned stimulus (US) onset (trace fear conditioning). To examine the role of the dorsal hippocampus in associating temporally discontiguous stimuli and to minimize the potential contribution of contextual cues, fear conditioning was conducted using a relatively short (3-s) trace interval. Inactivation of the dorsal hippocampus using the AMPA receptor antagonist NBQX (3 microg/hemisphere) or the GABA(A) agonist muscimol (5 microg/hemisphere) disrupted trace fear conditioning when conducted immediately following training.

Dissociable effects of hippocampus lesions on expression of fear and trace fear conditioning memories in rats.

The role of the hippocampus in memory is commonly investigated by comparing fear conditioning paradigms that differ in their reliance on the hippocampus. For example, the dorsal (septal) portion of the hippocampus is involved in trace, but not delay fear conditioning, two Pavlovian paradigms in which only the relative timing of stimulus presentation is varied. However, a growing literature implicates the ventral (temporal) portion of the hippocampus in the expression of fear, irrespective of prior training.

Timing of fear expression in trace and delay conditioning measured by fear-potentiated startle in rats.

In two experiments, the time course of the expression of fear in trace (hippocampus-dependent) versus delay (hippocampus-independent) conditioning was characterized with a high degree of temporal specificity using fear-potentiated startle. In experiment 1, groups of rats were given delay fear conditioning or trace fear conditioning with a 3- or 12-sec trace interval between conditioned stimulus (CS) offset and unconditioned stimulus (US) onset. During test, the delay group showed fear-potentiated startle in the presence of the CS but not after its offset, whereas the trace groups showed fear-potentiated startle both during the CS and after its offset.

Use of experimenter-given cues in visual co-orienting and in an object-choice task by a new world monkey species, cotton top tamarins (Saguinus oedipus).

Two methods assessed the use of experimenter-given directional cues by a New World monkey species, cotton top tamarins (Saguinus oedipus). Experiment 1 used cues to elicit visual co-orienting toward distal objects. Experiment 2 used cues to generate responses in an object-choice task.