Harry M. Sinnamon

The locus coeruleus: neurobiology of a central noradrenergic nucleus.

2. Anatomy of the nucleus locus coeruleus 2.

Double dissociation of spatial and object visual memory: evidence from selective interference in intact human subjects

A functional dissociation of the spatial and object visual systems was produced by selective interference in intact young adults. Subjects were instructed to remember the location of a dot in a spatial memory test, and the form of an object memory test. As predicted by current notions of dissociable visual systems in the primate, spatial memory was selectively impaired by a movement discrimination spatial task, whereas object memory was selectively impaired by a color discrimination object task.

Preoptic and hypothalamic neurons and the initiation of locomotion in the anesthetized rat

Despite its insensate condition and apparent motoric depression, the anesthetized rat can provide useful information about the systems involved in locomotor initiation. The preparation appears to be particularly appropriate for the study of the appetitive locomotor systems and may be more limited for the study of the circuits involved in exploratory and defensive locomotion. In the anesthetized rat, pharmacological evidence indicates that the preoptic basal forebrain contains neurons which initiate locomotor stepping. Mapping with low levels of electrical stimulation indicates, but does not prove, that a region centered in the lateral preoptic area might be the location of these neurons. Several lines of evidence indicate that locomotor stepping elicited by electrical stimulation of the hypothalamus is mediated by neurons in the perifornical and lateral hypothalamus. Locomotor effects of hypothalamic stimulation persist in the absence of descending fibers of passage from the ipsilateral preoptic locomotor regions but are severely impaired by kainic acid lesions in the area of stimulation. Injections of glutamate into the perifornical and lateral hypothalamus elicit locomotor stepping at short latencies. Anatomical evidence suggests that the two regions are components of a network for appetitive locomotion. The recognition that multiple systems initiate locomotion both clarifies and complicates the study of locomotion. It provides a framework that incorporates disparate findings but it also underscores the need for increased attention to behavioral issues in studies of locomotor circuitry.

Head movements elicited by electrical stimulation of the anteromedial cortex of the rat.

Electrical stimulation, 5-sec trains, 0.5 msec rectangular pulses, 20 Hz pulse frequency, was applied to the anteromedial cortex of awake rats (N = 28) to determine if head orienting behavior could be elicited. Following recovery from surgery in which up to six monopolar electrodes were implanted, the rats were adapted to and tested on a small platform surrounded by water. Elicited behavior patterns reliable at 150 microA or less in Experiment 1 (66 sites) and at 100 microA or less in Experiment 2 (32 sites) were analyzed. The most common response was a single head turn in a direction contralateral to the side of stimulation. Positive sites occurred throughout the anterior cingulate and the medial precentral regions. Coordinated forelimb movements were associated with contralateral head movements at dorsal anterior cingulate sites. Ipsilateral head turns were elicited at sites in the most rostral and ventral parts of the anteromedial cortex, including the prelimbic area. Lateral scanning sites were widespread but tended to concentrate at the mergence of the contralateral and ipsilateral movement fields. Vertical movements were often elicited with ipsilateral movements; dorsal sites supported downward head movements and ventral sites supported upward head movements. Sites supporting forward head movements were concentrated in the anterior cingulate region caudal to the genu of the corpus callosum. Neck extension usually appeared in conjunction with lateral head movements and frequently with forelimb movements.

SINGLE UNIT RECORDING IN THE MIDBRAIN OF RATS DURING SHOCK-ELICITED FIGHTING BEHAVIOR

Single unit activity was recorded extracellularly from the midbrain of rats during fighting behavior and during non-fighting control manipulations. Fighting behavior was elicited by footshock or startle stimuli or occurred spontaneously as a result of prior footshock presentations. Seven cells were found in the midbrain reticular formation and central gray which displayed maximum firing rates during fighting behavior. These cells also fired to a limited extent to some of the control manipulations, particularly contralateral vibrissae stimulation. These cells fired phasically during fighting behavior and their firing was correlated with either the approach or paw-strike of the opponent animal or to the response of the recording animal to a tactic of the opponent animal. However, no specific movement or sensory event reliably predicted the firing of these cells during fight sequences. Cells located in other midbrain areas, such as the deep tectum or the area of the red nucleus, also responded during fighting behavior. However, the discharge of these cells was correlated with specific body movements or sensory events. The activity during fighting was similar in rate and pattern to activity during control manipulations whenever similar movements or sensory stimulation were produced. Cells were also found which did not discharge during fighting behavior although they fired under a variety of other conditions.

Forelimb and hindlimb stepping by the anesthetized rat elicited by electrical stimulation of the pons and medulla

This study determined the lower brainstem sites at which electrical stimulation elicits stepping movements of the forelimbs and hindlimbs. Rats (N = 45), anesthetized with nembutal, were fixed in a stereotaxic apparatus so that their limbs contacted a moving treadmill belt. Electrical stimulation (100 microA, 10-sec trains, 0.5-msec cathodal pulses, 50-Hz pulse frequency) was applied every 200 micron through 173 movable electrodes. Well coordinated quadrupedal stepping was elicited by stimulation at dorsal posterior mesencephalic sites including the inferior collicular commissure, the central gray, the nucleus cuneiformis and lateral aspects of the pedunculopontine tegmental nucleus. Caudal and ventral to this general region, sites supporting quadrupedal stepping appeared mainly in or near the spinal trigeminal nucleus. Stepping with only the forelimb and hindlimb contralateral to the stimulation site was associated with the corticospinal tract, the lateral pontis oralis, the lateral pontis caudalis and the ventral reticular nucleus of the medulla. Bilateral forelimb stepping was associated with the trigeminal system and the gigantocellular reticular nucleus. At the level of the rostral medulla, systems involved in bilateral forelimb stepping and contralateral hindlimb stepping appear to be located medially. Systems concerned with bilateral hindlimb stepping appear to be located laterally.

Forelimb and hindlimb stepping by the anesthetized rat elicited by electrical stimulation of the diencephalon and mesencephalon.

Thirty rats anesthetized with a combination of chloralose, urethane and nembutal or nembutal alone were fixed in a stereotaxic apparatus and suspended over a moving treadmill belt. Electrical stimulation (100 microA, 10-sec trains, 0.5-msec cathodal pulses, 50-Hz pulse frequency) was applied every 200-microns through 109 movable electrodes. The patterns of stepping elicited ranged from well-coordinated stepping of all four limbs to spastic stepping of only one limb. In the hypothalamus, stepping-positive sites were found in and dorsal to the medial forebrain bundle, the paraventricular, dorsomedial and posterior nuclei, and the supramammillary areas. Dorsally, effective regions extended to the medial zona incerta and the fields of Forel. In the thalamus only the parafascicular nucleus and the anterior parts of the rhomboid and reuniens nuclei were positive. Positive sites were particularly dense in the ventral tegmental area. In the dorsal midbrain positive sites were most common at caudal levels dorsal and dorsolateral to the central gray. At sites in the area of the medial raphe, stepping was elicited only at the offset of the train. The distribution of positive sites resembled that found in unanesthetized rats and indicates that pathways at which electrical stimulation elicits stepping are separated into dorsal and ventral systems at the level of the midbrain.

Catecholaminergic and cholinergic agents and duration regulation of ICSS in the rat

Abstract ICSS in the diencephalon and midbrain was measured in a preferred duration situation as a function of pulse frequency and various pharmacological agents. Response measures were ON Time, the mean time ICSS was maintained; OFF Time, the mean time between the offset of a train and the initiation of the next; the log-log slopes of these two measures as a function of frequency; and Percentage Time ON. In both a shuttlebox (N = 13) and in an operant chamber (N = 10), Haloperidol (0.050 and 0.075 mg/kg) consistently decreased Percentage Time ON by elevating OFF times without consistent effects were greater at lower frequencies in the shuttlebox. Phentolamine (5 and 10 mg/kg), tested with 9 sites in the shuttlebox and 10 sites in the operant chamber, also differentially increased OFF Times with consistently greater effects at low frequencies. Evidence was not found for regional selectivity in the action of phentolamine or haloperidol among middle levels of the median forebrain bundle (MFB), the dorsal hypothalamus, the posterior MFB and the substantia nigra. Scopolamine (0.25, 0.50, and 1.00 mg/kg, six sites) and propranolol (10 and 15 mg/kg, seven sites) produced no consistent effects. FLA-63 (10 and 25 mg/kg, eight sites) produced some disruptions of performance at low frequencies but was without consistent effects. The results are consistent with a model of ICSS which includes a reward maintenance process, insensitive to catecholaminergic agents, and an approach-facilitation process which involves α-noradrenergic and dopaminergic systems.

ACTIVITY OF BASAL FOREBRAIN NEURONS IN THE RAT DURING MOTIVATED BEHAVIORS

The activity of single neurons in the basal forebrain was recorded in the freely-moving rat with moveable fine-wire electrodes. Neural activity was observed while the water-deprived male rat was exposed to three different types of motivating stimuli that elicit locomotion in a running wheel: an estrous female rat; a drinking tube containing water; and grasping and lifting by the experimenter. The neural activity was also observed when the subject was presented with standardized sensory tests and during single pulse stimulation of other brain structures. A majority of the 76 neurons recorded in the forebrain changed their firing rate during orienting and/or locomotion in general (23 neurons) or during behavior related to only one of the specific motivational contexts: the conspecific female (4 neurons); water (7 neurons); or grasp by the experimenter (8 neurons). Whereas the neurons related to orienting and/or locomotion in general were scattered through various brain structures, those neurons related to specific motivational contexts were concentrated in specific areas: the sexually dimorphic nucleus of the medial preoptic area (conspecific female); lateral septum (water); and lateral preoptic area (water and grasp). The present results, although based on relatively few neurons, are consonant with results of research using other techniques. This indicates that analyses at the level of the single neuron promise to be useful for understanding the role of the basal forebrain in motivational systems.

Locomotion elicited by lateral hypothalamic stimulation in the anesthetized rat does not require the dorsal midbrain

Locomotor stepping elicited by lateral hypothalamic stimulation in the anesthetized rat is blocked by lesions in the anterior ventromedial midbrain. This study determined in acute experiments whether the dorsal midbrain regions implicated in locomotion were also part of the necessary pathway. Rats were anesthetized with Nembutal and held in a stereotaxic apparatus so that stepping responses rotated a wheel. Stepping was elicited by stimulation of the lateral hypothalamus (up to 100 microA, 0.5 ms cathodal pulses, 50 Hz, 10-s train length). Nine rats received unilateral lesions ipsilateral to the locomotor electrode and 3 rats received bilateral lesions. None of the dorsal midbrain lesions reduced locomotion elicited by ipsilateral lateral hypothalamic stimulation. Therefore the following regions are unnecessary for this type of locomotion: the dorsal and lateral central gray, the tegmentum lateral to the central gray, and in particular the area cuneiformis and the dorsal aspect of the pedunculopontine region. The neural systems required for lateral hypothalamic locomotion are located ventral to the superior cerebellar peduncle.