Increased oxidative metabolism in middle suprasylvian cortex following removal of areas 17 and 18 from newborn cats

We measured changes in metabolic activity in middle suprasylvian (MS) cortex of cats subjected to early or late removal of areas 17 and 18 to localize shifts in activity possibly indicative of regions within MS cortex that may receive expanded inputs and be involved in the sparing of some visual behaviors following early primary visual cortex damage. Cytochrome oxidase (CO) activity was measured in MS cortex of mature, intact cats and of others with areas 17 and 18 removed in adulthood (P180), or on postnatal day 28 (P28) or postnatal day 1 (P1). Not less than 9 months after the ablation, brain sections were prepared and reacted for the presence of CO. The density of CO reactivity in each of the six cortical layers in MS cortex was measured and standardized against densities from ventral periaqueductal gray or hypothalamus on the same section. Following lesions on P1, significant increases in CO activity occurred in deep layer III and in layer IV of the medial bank of the MS sulcus, including all of area PMLS and the posterior portion of AMLS. In contrast, there were no significant differences in the level of CO activity among P28, P180, or intact cats for any of the cortical layers, and all had lower levels than the P1 cats. This metabolic change provides an anatomical marker for localizing adjustments in MS cortex and can be linked to amplified projections into MS cortex from the thalamus (LPm and A and C laminae of the dorsal lateral geniculate nucleus) and ventral posterior suprasylvian cortex following P1 ablations. Furthermore, this neurochemical analysis implicates a distinct region of MS cortex as the cortical locus of some spared visual functions following early primary visual cortex damage.     

Responses of presumed cholinergic mesopontine tegmental neurons to carbachol microinjections in freely moving cats

Summary The effects of microinjections of a cholinergic agonist, carbachol (0.2 g/0.2 l), were examined on three different types of rostrally projecting tonic neurons that we have reported previously in the dorsal part of the pontomesencephalic tegmentum known to contain numerous cholinergic cell bodies: 1) tonic type I slow (Type I-S); 2) tonic type I rapid (Type I-R); and 3) tonic type II (Type II) (El Mansari et al. 1989). Microinjections of carbachol near unit recording sites in freely moving cats induced within a few minutes a complete suppression of the spontaneous activity and a marked reduction in orthodromic excitation of identified and non-identified type I-S neurons. These effect lasted for approximately 90–120 min and were reversed by local (0.4 g/0.2 l) or systemic (0.1–0.2mg/kg, i.m.) administration of atropine sulfate. In contrast, the cholinergic agonist had no consistent effects on tonic type II nor on tonic type I-R neurons. In the light of these and other recent findings, we suggested the direct inhibition of central cholinergic neurons via muscarinic receptors, on the one hand, and the cholinergic nature of type I-S, but not type I-R nor type II neurons, on the other.     

Effects of VMH lesions on CAR learning in cats

Cats with lesions in the ventromedial hypothalamus learned a two-way shuttle avoidance task faster than normal controls did when the shock US was relatively low. When shock US was relatively high, cats with these lesions showed immobility behavior, and an impaired CAR. Although the passive avoidance deficit may be involved, the reduced fear hypothesis is preferred.     

Unitary characteristics of presumptive cholinergic tegmental neurons during the sleep-waking cycle in freely moving cats

Summary A total of 260 neurons were recorded in the rostral pontine tegmentum of freely moving cats during the sleep-waking cycle. Of these, 207 neurons (80%) were located in the dorsal pontine tegmentum containing monoaminergic and choline acetyltransferase (ChAT)-immunoreactive, or cholinergic neurons. In addition to presumably monoaminergic PS-off cells (n = 51) showing a cessation of discharge during paradoxical sleep (PS) and presumably cholinergic PGO-on cells (n = 40) exhibiting a burst of discharge just prior to and during ponto-geniculo-occipital (PGO) waves, we observed tonic (n = 108) and phasic (n = 61) neurons exhibiting, respectively, tonic and phasic patterns of discharge during wakefulness and/or paradoxical sleep. Of 87 tonic cells histologically localized in the dorsal pontine tegmentum rich in cholinergic neurons, 46 cells (53%) were identified as giving rise to ascending projections either to the intralaminar thalamic complex (n = 26) or to the ventrolateral posterior hypothalamus (n = 13) or to both (n = 9). Two types of tonic neurons were distinguished: 1) tonic type I neurons (n = 28), showing a tonic pattern and high rates of discharge during both waking and paradoxical sleep as compaired with slow wave sleep; and 2) tonic type II neurons (n = 20), exhibiting a tonic pattern of discharge highly specific to the periods of paradoxical sleep. Tonic type I neurons were further divided into two subclasses on the basis of discharge rates during waking: a) rapid (Type I-R; n = 17); and b) slow (Type I-S; n = 11) units with a discharge frequency of more than 12 spikes/s or less than 5 spikes/s, respectively. Like monoaminergic PS-off and cholinergic PGO-on cells, both tonic type II and type I-S cells were characterized by a long spike duration (median: 3.3 and 3.5 ms), as well as by a slow conduction velocity (median: 1.8 and 1.7 m/s). In the light of these data, we discuss the possible cholinergic nature and functional significance of these ascending tonic neurons in the generation of neocortical electroencephalographic desynchronization occurring during waking and paradoxical sleep.     

Eating banana in cats for brain stimulation reward

Hungry cats offered banana and meat pellets, preferred banana to meat pellets when electrical stimulation in the hypothalamus (ESB) was delivered for consumption of banana but never for consumption of meat pellets. Withholding ESB caused the cessation of banana consumption which was resumed with the reapplication of ESB. When, after a few weeks of training, both foods were presented to the hungry cats in their home compartment, without ESB, the animals approached banana and ignored meat pellets.     

Comparative commissure function: Interocular transfer of successive visual discriminations in cats

Intact and chiasm-sectioned cats were tested for interocular transfer after monocular training of a successive two-choice discrimination task. Similar tasks were previously employed to demonstrate complete failure of interocular transfer in both commissure-intact pigeons and goldfish. In contrast, both groups of cats showed clear interocular transfer. The results provide evidence for differing functional capacity in analogous interhemispheric pathways among vertebrates, and suggest that interocular transfer of successive visual discriminations may be a suitable paradigm for study of phyletic differences in behavioral ability.     

Feeding induced in cats by electrical stimulation of the brain stem

Summary Stimulation at 14 of 106 loci (Figs. 1 and 2) at which electrodes had been chronically implanted elicited immediate feeding in fully satiated, freely moving cats. Half of the effective points were in the lateral hypothalamus and thus agreed with expectations from extensive prior research on the neural organization of feeding behavior. The other points, however, were in the ventral tegmental area or at the ventrolateral boundary of the central gray. The distribution of all effective points could be explained as following a projection pathway from the globus pallidus. Exploration along 162 recording tracks in acute experiments on these same cats revealed no consistent differences in projection of evoked potentials which could distinguish stimulation at effective versus ineffective loci. Potentials of possible significance, however, were evoked in the paramedial nucleus reticularis of the medulla, the rostral pontine nuclei, the nucleus centralis superior of Bekterev, the lateral frontal cortex and the basal medial forebrain in the vicinity of the diagonal band of Broca.Supported by USPHS Grant B 1068. Dr. Wyrwicka held a fellowship from Foundations' Fund for Research in Psychiatry. The authors are indebted to Mr. Joseph Jones and Mrs. Frances Bignall for technical assistance.     

Visual perception in cats after environmental surgery

Summary This report describes a series of experiments testing the behavioral significance of orientation sensitive cells in the cat's visual cortex. Cats used for this purpose were raised with one eye (VE) viewing a field of vertical lines and the other eye (HE) viewing a field of horizontal lines. This experience simplified their cortical physiology, and is thus called environmental surgery. Cells with elongated fields were found to be activated monocularly: those driven by the VE had vertically oriented receptive fields, while those activated by the HE had horizontally oriented fields. These animals were tested, using one eye at a time, on a series of visual discriminations: a) flux discrimination, b) tests for selective response to vertical and horizontal lines, c) discrimination between two lines differing only in orientation, d) discrimination between mirror image stimuli, and e) evaluation of inter-ocular transfer on these discriminations. The threshold tests for orientation discrimination gave the clearest results: there were small but consistent differences in performance between the VE and HE which depended on the orientation of the lines being discriminated. There was also evidence that the animals responded to different parts of a stimulus with the VE and HE. As a group, the experimental cats showed less interocular transfer of visual discriminations than the normal controls. However, surprisingly, there was also evidence for much functional equivalence between the two eyes. Possible explanations for this are considered and it is suggested that an animal's ability to make pattern discriminations is not rigidly determined by the shape and orientation of its receptive fields.     

Insular-temporal lesions and vibrotactile temporal pattern discrimination in cats

Cats were trained in a double-grill box to discriminate a change in the temporal pattern of ongoing vibrotactile pulses at two different intensities. Animals acquiring the discrimination were prepared with bilateral insular-temporal lesions. The temporal pattern discrimination was lost postoperatively, and could not be reestablished even after prolonged. A simple vibrotactile intensity discrimination could be learned postoperatively, indicating that the impairment on the temporal pattern task was not due to a general deficit in associative learning. Earlier research has been reported which implicates the insular-temporal region in visual temporal pattern discrimination. Considered in conjunction with this earlier work, the present data suggest that insular-temporal cortex is a multimodal area concerned with the perception of temporal patterns of stimuli.     

Delayed response in cats after frontal lesions extending beyond the gyrus proreus

The experiment tested the hypothesis that the consistently smaller impairment of delayed responding after prefrontal ablations in cats as compared to monkeys may be attributed to incomplete lesions of the projection area of the mediodorsal thalamic nucleus in the cat. The results disconfirmed the hypothesis: cats with ablations of both the gyrus proreus and the periproreal cortex (excluding the precruciate area) showed some savings in retention of delayed responses and were not more severely impaired than the cats with lesions restricted to the gyrus proreus. Cats are less dependent on an intact frontal cortex for performance of delayed responses than are adult monkeys. No evidence was found that the frontal cortical mechanism mediating delayed responses in the cat extends beyond the gyrus proreus.or can be described by the focus and field paradigm.     

Artificial Selection for Increased Maternal Defense Behavior in Mice

Maternal aggression is directed towards intruders by lactating females and is critical for defense of offspring. Within-family selection for increased maternal defense in outbred house mice (Mus domesticus; Hsd:ICR strain) was applied to one selected (S) line, using total duration of attacks in a 3-min test as the selection criterion. One control (C) line was maintained and both lines were propagated by 13 families in each generation. Prior to selection, heritability of maternal aggression was estimated to be 0.61 based on mother-offspring regression. Duration of attacks responded to selection with a mean realized heritability of 0.40 (corrected for within-family selection) after eight generations. At generation 5, the S and C line also differed significantly for litter size at birth and at mid-lactation (both lower in S), average individual pup mass at mid-lactation (higher in S), and pup retrieval latency (longer in S), but not for other maternal measures that we studied (e.g., dam mass). Additionally, number of entries to middle and closed plus maze compartments was significantly higher in S mice in Generation 5. This is the first study to select for high maternal defense and these mice will be made available as a tool for understanding the genetic and neural basis of maternal aggression.     

The coding of head orientations in neurons of bilateral vestibular nuclei of cats after unilateral labyrinthectomy: response to off-vertical axis rotation

 In decerebrate cats that had been acutely hemilabyrinthectomized (HL), the extracellular activities of vestibular nuclear neurons on the lesioned and labyrinth-intact sides were studied during constant-velocity off-vertical axis rotations (OVAR) in the clockwise (CW) and counterclockwise (CCW) directions (at 10° tilt). Over the range of 1.75–15°/s, two types of neuronal responses were identified on both sides. Some neurons showed symmetric and velocity-stable bidirectional response sensitivity (δ defined as the CW gain over the CCW gain) while other neurons exhibited asymmetric and velocity-variable δ. The mathematically derived gain tuning ratios of these two groups of neurons were within the range of one-dimensional and two-dimensional neurons respectively. The best response orientations in one-dimensional neurons and the orientations of the maximum response vector, S _max, in two-dimensional neurons were found to point in all directions on the horizontal plane. On the labyrinth-intact side, both the one-dimensional and two-dimensional neurons showed asymmetry in the neuron numbers and/or the response gains between the two roll quadrants as well as between the two pitch quadrants. In addition, both the neuron number and gain were significantly higher for neurons in the head-down/ipsilateral-side-down half-circle than those in the head-up/contralateral-side-down half-circle. None of the aforementioned asymmetries was observed on the lesioned side. That a comparable pattern of distribution was observed in the one-dimensional and two-dimensional neurons suggests that these neurons maintain a common spatial reference frame in encoding head orientational signals arising from the ipsilateral and contralateral otoliths. Furthermore, a predominance of two-dimensional neurons that exhibited a greater gain with CW rotations was observed on both sides of HL cats. Of the response dynamics observed amongst neurons on the two sides of HL cats, no difference was found with regard to the response gain and the pattern of response lead. However, a difference in response lag was observed between neurons on the two sides of HL cats. These suggest that there is a segregation of otolithic signals to reach the ipsilateral and contralateral vestibular nuclei. Taken together, the present study demonstrates that one-dimensional and two-dimensional neuronal responses could be elicited with inputs arising solely from the ipsilateral or contralateral otoliths. The observed orientational tuning and the CW-CCW asymmetry to bidirectional rotation may provide the essential directional coding of head orientations. Further, the imbalance of spatial/dynamic response patterns between the bilateral vestibular nuclei following the restriction of otolith inputs by HL implies that converging otolithic inputs from the bilateral labyrinths are essential for producing the neuronal responses in control animals. The results are also discussed in terms of the possible contribution of the various neural asymmetries between neuronal subpopulations in the bilateral vestibular nuclei to the behavioral symptoms accompanying acute HL. Received: 1 March 1996 / Accepted: 20 September 1996     

Vestibulo-ocular reflex adaptation in cats before and after depletion of norepinephrine

Summary The vestibulo-ocular reflex (VOR) operates to stabilize the eyes in space during movements of the head. The system has been described as having a gain of approximately -1 since stimulation of the semi-circular canals brought about by head movements will have the effect of causing the eyes to rotate an equal amount in the opposite direction. Change in the gain of the VOR has been put forth as a model to study plasticity in the central nervous system. Since numerous studies have implicated norepinephrine (NE) in neuroplasticity and modifiability of neural circuits, we attempted to determine the effect of NE depletion (via 6-hydroxydopamine (6-OHDA) intra-cisternal injection) on the modifiability of the VOR. We have found that cats increase the gain of their VOR over a four hour period when rotated in the horizontal plane in a manner equal but opposite to the rotation of a surrounding opto-kinetic drum. The entire group of animals manifests a statistically significant decrement in their ability to increase VOR gain when central stores of norepinephrine are depleted via intra-cisternal injection of 6-OHDA. Individual animals manifest a wide variety of gain changes (0.98 to 1.62). We have found that there were two groups of cats — high and low gain modifiers. The greatest reduction in VOR gain increase after NE depletion was observed in the high gain modifiers. No difference was observed in the low gain modifiers. These same animals tested for VOR modification after amphetamine injection, produced similar results. Alertness during the VOR modification task, as estimated by saccadic eye movement counts, was unchanged after NE depletion. NE levels, measured by HPLC-EC, after depletion were reduced to the greatest extent in the cerebellum. There was also a substantial reduction of NE in the visual cortex with less of a reduction in the brain stem.     

Excitation of the extraocular muscles in decerebrate cats during the vestibulo-ocular reflex in three-dimensional space

Summary (1) Vestibulo-ocular reflex excitation of the six extraocular muscles was studied by recording their electromyographic activity in decerebrate cats during oscillations about horizontal and vertical axes, at frequencies from 0.07 to 4 Hz. Animals were oriented in many different positions and rotated about axes that lay in the horizontal, frontal, or sagittal planes defined by our coordinate system. (2) The strengths of modulation (gains) of the responses of all extraocular muscles were a sinusoidal function of the orientation of the rotation axis within a coordinate plane, and this function was nearly independent of rotation frequency. (3) The responses were used to determine an axis of maximal excitation for each of the extraocular muscles by the vestibulo-ocular reflex. Antagonistic muscle pairs were found to have best axes in nearly opposite directions, confirming their operation as pairs. (4) Excitation of the medial and lateral rectus could be explained by input from the paired horizontal semicircular canals, with essentially no convergent input from vertical canals. (5) Excitation of the vertical rectus and oblique muscles could be explained by convergent inputs from the vertical canals with little or no horizontal canal input.     

Discharge properties of medullary reticulospinal neurons during postural changes induced by intrapontine injections of carbachol,atropine and serotonin,and their functional linkages to hindlimb motoneurons in cats

The present study was aimed at elucidating the pontomedullary and spinal cord mechanisms of postural atonia induced by microinjection of carbachol and restored by microinjections of serotonin or atropine sulfate into the nucleus reticularis pontis oralis (NRPo). Medullary reticulospinal neurons (n=132) antidromically activated by stimulating the L1 spinal cord segment were recorded extracellularly. Seventy-eight of them were orthodromically activated with mono- or disynaptic latencies by stimulating the NRPo area at the site where carbachol injections effectively induced postural atonia. Most of these reticulospinal neurons (71 of 78) were located in the nucleus reticularis gigantocellularis (NRGc). Following carbachol injection into the NRPo, discharge rates of the NRGc reticulospinal neurons (29 of 34) increased, while the activity of soleus muscles decreased bilaterally. Serotonin or atropine injections into the same NRPo area resulted in a decrease in the discharge rates of the reticulospinal neurons with a concomitant increase in the levels of hindlimb muscle tone. Membrane potentials of hindlimb extensor and flexor alpha motoneurons (MNs) were hyperpolarized and depolarized by carbachol and serotonin or atropine injections, respectively. In all pairs of reticulospinal neurons and MNs (n=11), there was a high correlation between the increase in the discharge rates and the degree of membrane hyperpolarization of the MNs. Spike-triggered averaging during carbachol-induced atonia revealed that inhibitory postsynaptic potentials (IPSPs) were evoked in 15 MNs by the discharges of nine reticulospinal neurons. Four of them evoked IPSPs in more than one MN. The mean segmental delay and the mean time to the peak of IPSPs were 1.6 ms and 2.0 ms, respectively. Axonal trajectories of reticulospinal neurons (n=6), which evoked IPSPs in MNs, were investigated in the lumbosacral segments (L1-S1) by antidromic threshold mapping. The stem axons descended through the ventral (n=2) and ventrolateral (n=4) funiculi in the lumbar segments. All axons projected their collaterals to the intermediate region (laminae V, VI) and ventromedial part (laminae VII, VIII) of the gray matter. All these results suggest that the reticulospinal pathway originating from the NRGc is involved in postural atonia induced by pontine microinjection of carbachol, and that the pathway is inactivated during the postural restoration induced by subsequent injections of serotonin or atropine. It is further suggested that the pontine inhibitory effect is mediated via segmental inhibitory interneurons projecting to MNs.     

Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in the periaqueductal gray after exposure to an innate fear stimulus

Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in the periaqueductal gray after exposure to an innate fear stimulus--nitric oxide (NO) acts as a neurotransmitter in the rat dorsolateral periaqueductal gray (dlPAG), a midbrain structure that modulates fear and defensive behavior. Since defensive reactions can be alleviated by anxiolytic/anti-panic drugs, the present study tested the effect of clomipramine, a serotonin re-uptake inhibitor, on the activation of NO-producing neurons in the dlPAG of rats exposed to a live predator. Double staining was performed using Fos immunohistochemistry and NADPH-diaphorase as techniques to mark neural activation and to detect NO-producing neurons, respectively. Male Wistar rats received acute or chronic (21 days) injections of saline or clomipramine (10 or 20 mg/kg/day) and were exposed to a live cat. The animals exhibited a robust defensive reaction accompanied by an increase in the number of Fos- and double-stained neurons in the dlPAG, suggesting that cat exposure activates NO-producing neurons. Such effects were not significantly attenuated by clomipramine treatments. The intensity of fear reaction correlated with the intensity of neural staining in the dlPAG, regardless the drug treatment. Thus, the present results reinforce the hypothesis that NO may coordinate defensive responses in the dlPAG and indicate that this mechanism may not be modulated by a serotonin re-uptake inhibitor.     

Increased c-fos expression in the central nucleus of the amygdala and enhancement of cued fear memory in Dyt1 ΔGAG knock-in mice

DYT1 dystonia is caused by a trinucleotide deletion of GAG (ΔGAG) in DYT1, which codes for torsinA. A previous epidemiologic study suggested an association of DYT1 ΔGAG mutation with early-onset recurrent major depression. However, another study reported no significant association with depression, but instead showed an association with anxiety and dystonia. In this study, we analyzed these related behaviors in Dyt1 ΔGAG heterozygous knock-in mice. The knock-in mice showed a subtle anxiety-like behavior but did not show depression-like behaviors. The mutant mice also displayed normal sensorimotor gating function in a prepulse inhibition test. While normal hippocampus-dependent contextual fear memory and hippocampal CA1 long-term potentiation (LTP) were observed, the knock-in mice exhibited an enhancement in the formation of cued fear memories. Anatomical analysis indicated that the number of c-fos positive cells was significantly increased while the size of the central nucleus of the amygdala (CE) was significantly reduced in the knock-in mice. These results suggest that the Dyt1 ΔGAG mutation increased the activity of the CE and enhanced the acquisition of the cued fear memory.     

Anatomical correlates of return of locomotor function after partial spinal cord lesions in cats

Summary We trained cats to walk on a moving treadmill belt, then subjected them to partial transverse sections of the thoracic spinal cord. Afterwards, we observed their ability to walk on the treadmill, over a period of several weeks, using gait analysis techniques to describe the resultant deficits. The extent of the lesions was verified histologically, and the identity of the spared descending axons from the brain stem was demonstrated by retrograde labeling with horseradish peroxidase.We found that significant sparing or recovery of hindlimb locomotor function is closely linked to sparing of axons in at least one ventrolateral quadrant of the cord. The essential elements probably belong to vestibulospinal and reticulospinal systems.Supported in part by grants by the NINCDS (NS-14546) and the Paraplegia Foundation of ArizonaMedical Investigator of the Veterans Administration     

Attack,grooming, and threat elicited by stimulation of the pontine tegmentum in cats

Predatory-like biting attack and associated prey-kicking, grooming, and components of threat behavior were elicited by electrical stimulation of different, but partly overlapping areas of the pontine tegmentum in cats. Electrodes producing biting attack and prey-kicking were located in the central tegmentum. The effective area for grooming was located in the dorsolateral tegmentum and extended, with the superior cerebellar peduncle, into the deep fibers of the cerebellum. Electrodes producing threat responses were more widely distributed, but tended to be located ventrally or laterally. The results support the view that the lower brainstem may play an important role in the production of complex species-typical behaviors.     

Characteristics of target-reaching in cats III. Lifting and protraction with an obstacle in the movement path and after its removal

Three cats were trained to perform target-reaching to a horizontal tube with food placed at shoulder level, and the kinematic characteristics of the movements were investigated by recording the trajectory of the wrist. From the very onset of training, a vertical obstacle was placed in front of the cats. The obstacle forced the animals to perform movements with an initial phase dominated by limb-lifting to position the wrist above the obstacle, followed by a second phase of protraction towards the tube; in the sagittal plane, the movement paths were segmented with an upwards convexity. After a training period of 1 year (about 7000 movements), the obstacle was removed. All cats then quickly (within a few trials) changed the trajectory so that the main part of protraction now occurred in parallel with limb-lifting during the first half of the movement. The initial slope of the sagittal movement path became less steep and the upwards convexity less pronounced. Such trajectories, which predominated for several experiments after removal of the obstacle, were only slightly different from those observed in control cats not trained with an obstacle. The results are discussed in relation to a previously proposed hypothesis of motor “imprinting” during extensive training in a particular experimental paradigm. Received: 19 August 1996 / Accepted: 4 December 1997