Effects of systemic injection of neuroleptics on neuronal background activity in the cat ventrolateral thalamic nucleus

Background activity was recorded in 272 neurons of the ventrolateral thalamic nucleus before and after systemic haloperidol and droperidol injection at a cataleptic dose using intracellular techniques during chronic experiments on cats in a drowsy condition. Brief burster discharges lasting 5–50 msec and following on at a high intraburst spike rate (of 200–450 Hz) were characteristic of neuronal activity in intact animals. Regular discharges occurred at the rate of 2–2.5 Hz or occasionally 3–4 Hz in 15% of cells. Numbers of neurons with the latter activity pattern rose to 22 and 30%, respectively, following haloperidol and droperidol injection. Both irregular and prolonged (80–300 msec) regular discharges were recorded in one third of the total. A relatively low intraburst spike rate (of 60–170 Hz) was observed in 37% of cells following 10 days' haloperidol injection. These changes are thought to be produced by intensified inhibitory effects on neurons of the thalamic ventrolateral nucleus from the substantia nigra and reticular thalamic nucleus following blockade of dopaminergic and -adrenergic receptors.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 5, pp. 675–685, September–October, 1989.     

Spontaneous and evoked unit activity of the septum and hippocampus transplated into the rat neocortex

Embryonic septal and hippocampal tissue was transplanted into a cavity formed by removal of part of the parietal cortex of adult rats by suction. By extracellular recording 4–6 months after the operation cells with spontaneous activity with a frequency of 3.6±0.4 Hz, characterized by an irregular, stochastic spike distribution, were detected in the graft. About 90% of cells responded to electrical stimulation of neighboring cortical areas after a latent period of 5–43 msec. The most stable responses appeared to stimulation with frequencies of 5–10 Hz; in most cases the evoked discharge was followed by a period of inhibition of spontaneous activity (100–700 msec). The same number of cells responded to tactile stimulation of the body surface and vibrissae of the recipient animal. Specific responses of different types with latent periods of between 50 and 600 msec were observed. Normalization of unit activity of intracerebral grafts compared with activity of cells in tissue developing in the anterior chamber of the eye, and their functional integration with the recipient's brain are discussed.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 17, No. 2, pp. 160–168, March–April, 1985.     

Spontaneous unit activity in anterior (limbic) nuclei of rabbit thalamus

Spontaneous spike activity in three anterior (limbic) neurons of the thalamic nucleus was studied by means of extracellular recording during chronic experiments on anesthetized rabbits. Neurons of the anteroventral nucleus showed high mean rate (24.8±5.8 spikes/sec) and varying structure of spike discharges ("inactivating" bursts of discharges, modulations in delta- and theta-rhythms, and bursts of discharges with a spindle rhythm of 12–14 Hz). "Inactivating" bursts of discharges alternating with single discharges predominated in the activity of neurons of the anteromedial nucleus (mean rate 10.0±1.4 spikes/sec). Activity of the anterodorsal nucleus could be clearly distinguished by the predominance of high-frequency groups of spikes (mean group frequency 67±5 spikes/sec) with prolonged intervals between groups.Institute of Biological Physics, Academy of Sciences of the USSR, Puschino, Moscow Province. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 579–586, September–October, 1985.     

Neurons projecting from the brain to the corpora allata in orthopteroid insects: anatomy and physiology

Retrograde and orthograde labeling of neurons projecting to the corpus allatum was performed in locust, grasshopper, cricket, and cockroach species in order to identify brain neurons that may be involved in the regulation of juvenile hormone production. In the acridid grasshopper Gomphocerus rufus L., and the locusts Locusta migratoria (R.&F.) and Schistocerca gregaria Forskal, the corpora allata are innervated by two morphologically distinguishable types of brain neurons. One group of 9–13 neurons (depending on species) with somata in the pars lateralis extend axons via the nervus corporis cardiaci 2 and nervus corporis allati 1 to the ipsilateral corpus allatum, whereas two cells in each pars lateralis have bilateral projections and innervate both glands. No direct connection between the pars intercerebralis and corpus allatum has been found. In contrast, neurons with paired axons innervating both glands are not present in Periplaneta americana (L.) and Gryllus bimaculatus de Geer. Instead, two cells in each pars lateralis project only to the gland contralateral to their somata. Electrophysiological experiments on acridid grasshoppers have confirmed the existence of a direct conduction pathway between the two glands via the paired axons of four cells that have been identified by neuroanatomy. These cells are not spontaneously active under experimental conditions. Ongoing discharges in the left and right nerves are unrelated, suggesting that the corpora allata receive independent neuronal inputs from the brain.     

Effects of sombrevine on orientational tuning of visual cortex neurons in the cat

Changed orientational tuning (OT) in 58 visual cortex units was investigated during acute experiments on immobilized cats under light short-lasting sombrevine-induced anesthesia. A 47.6±5.6° alteration in the preferred orientation of 60% of cells occurred following sombrevine injection but no change occurred at any stage of anesthesia in the remainder. The latter group showed a preference for horizontal and vertical orientations, less pronounced in the former category. "Stable" neurons also displayed less acute tuning and more selective detection in comparison with "unstable" units. Breadth of orientational tuning consistently changed by an average of 65.2±6.7° in 55% of neurons, while tuning deteriorated in 31% and sharpened in 24% of cells. No regular change in tuning band occurred in the remainder. Background firing rate and evoked spike activity declined by 58% and 35%, respectively under anesthesia in 2/3 of the cells tested. Tuning bandwidth of unit firing rate had generally recovered within 20–40 min after administering the anesthetic (i.e., as the anesthesia wore off).Higher Nervous Activity and Neurophysiology Research Institute. Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 21, No. 6, pp. 812–820, November–December, 1989.     

Responses of upper cervical spinal neurons in cats to stimulation of the brain-stem locomotor region at different frequencies

Synaptic responses of neurons in segments C₂ and C₃ to stimulation of locomotor points in the medulla or midbrain were recorded extracellularly in mesencephalic cats. Neurons generating responses with an index of 0.4–0.6 to stimulation with a frequency of 2 Hz maintained this same index at frequencies of 20–60 Hz. The discharge index of many neurons during stimulation at 2 Hz was low, and it increased to 0.4–0.6 when high-frequency stimulation was used. More than half of the cells were excited by stimulation of both ipsilateral and contralateral locomotor points; one-quarter of the neurons responded to stimulation of locomotor points in both medulla and midbrain. The cells studied were located 1.8–4.2 mm from the dorsal surface of the spinal cord. The mean latencies of responses with an index of not less than 0.5 lay within the range 2–30 msec, with a mode of 2–8 msec. Considerable fluctuations of latent period were observed for long-latency responses. The possibility that the neurons studied may participate in the transmission of activity from the locomotor region of the brain stem to stepping generators in the spinal cord is discussed.Institute for Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 15, No. 4, pp. 355–361, July–August, 1983.     

Sister chromatid exchange in murine alveolar macrophages,regenerating liver and bone marrow cells — a simultaneous multicellular in vivo assay

Differential labeling of sister chromatids was achieved simultaneously in murine alveolar macrophages, regenerating liver, and bone marrow cells of partially hepatectomized mice as well as in alveolar macrophages and bone marrow cells of nonhepatectomized mice. The mean frequency of SCE/cell ±S.D. and the percentage of second division cells for each cell type were determined. No significant differences in mean frequencies of SCE/cell were observed among the cell types or between hepatectomized (alveolar macrophages –3.6±2.2, bone marrow –3.4±2.2; regenerating liver –3.6±2.4) and nonhepatectomized (alveolar macrophages —3.4 ±1.9; bone marrow —2.9±1.8). Although the percentage of second division cells was dependent upon cell type, no significant differences were apparent between hepatectomized (alveolar macrophages —57±8%; bone marrow —37±6%; regenerating liver –65±6%) and nonhepatectomized mice (alveolar macrophages –53±6%; bone marrow –36±4%). Comparisons between BrdU treated and nontreated nonhepatectomized mice revealed no significant alteration in mitotic yields.     

Electrophysiological properties of neurons and neuronal organization of the crayfish somatogastric ganglion

Experiments with intracellular recording from neurons of the isolated crayfish somatogastric ganglion established that the membrane potential of the neurons is 53±3 mV. Single stimulation of the central branches of the ganglion evoked EPSP and a spike in the neurons. The spike amplitude was 7.5±0.6 mV. The small amplitude of the spike is explained by the fact that it arises at some distance from the body of the neuron and propagates electrotonically in it. Summation of several EPSP is necessary in most cases for initiation of the spike. When the orthodromic stimulus was strong enough, and IPSP occurred in some cells in addition to the EPSP and spike. Stimulation of the peripheral nerves of the ganglion induced in most neurons antidromic excitation and in some neurons orthodromic excitation. Some neurons spontaneously discharged rhythmically with an unstable frequency (11–27 impulses/sec). An investigation of the effect on neurons of chemical agents [acetylcholine, adrenalin, noradrenalin, gamma-aminobutyric acid (GABA), glutamic acid, and dopamine] showed that acetylcholine has the strongest and most stable depolarizing action and apparently is a synaptic transmitter in the ganglion. The other agents excited some neurons — depolarized them and evoked rhythmic discharges — and, coversely, hyperpolarized and suppressed the rhythmic activity of other neurons. A scheme of neuronal organization of the somatogastric ganglion of the crayfish is proposed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No. 3, pp. 307–313, May–June, 1970.     

Two patterns of bulbar neuronal response to microstimulation of locomotor and inhibitory brain stem sites

Synaptic responses (postsynaptic potentials and action potentials) were evoked in mesencephalic decerebellated cats by stimulating pontine bulbar locomotor and inhibitory sites (LS and IS, respectively) with a current of not more than 20 µA in "medial" and "lateral" neurons of the medulla. Some neurons even produced a response to presentation of single (actually low — 2–5 Hz — frequency) stimuli. The remaining cells responded to stimulation at a steady rate of 30–60 Hz only. Both groups of medial neurons were more receptive to input from LS. Lateral neurons responding to even single stimuli reacted more commonly to input from LS and those responding to steady stimulation only to input from IS. Many neurons with background activity (whether lateral or medial) produced no stimulus-bound response, but rhythmic stimulation either intensified or inhibited such activity. This response occurs most commonly with LS stimulation. Partial redistribution of target neurons in step with increasing rate of presynaptic input may play a major part in control of motor activity.Institute for Research into Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 257–266, March–April, 1990.     

Immunosuppressor activity of rat endometrial granulated cells and their differentiation

Natural killer and natural suppressor activities of the rat endometrial granulated cells were assayed on days 13 and 14 of pregnancy or pseudopregnancy. Metrial gland granulated cells were used as endometrial granulated cells. The natural killer activities of metrial gland granulated cells and other cells were determined by means of Hashimoto-Sudo test with K562 cells as targets. The estimation of natural killer activity included removal of the cells sticking to glass from a suspension of material gland granulated cells. Cytochemically, metrial gland granulated cells were identified by the presence of PAS-positive granules in the cytoplasm after treatment of the cells with diastase and identification of a specific antigen with the help of specific antisera. The natural killer activity of metrial gland granulated cells was twice weaker than that of splenocytes from the same pregnant or pseudopregnant females. The level of natural killer activity was proportional to the content of metrial gland granulated cells in a cell system. These data suggest that the natural killer activity of metrial gland granulated cells is realized via their contact with cell targets. Natural killer and suppressor activities were determined simultaneously for metrial gland granulated cells and splenocytes of the same rat with common cell targets. When estimating the natural suppressor activity of metrial gland granulated cells, the splenocytes of the same rat were used as an effector in a natural killer test. Various amounts of metrial gland granulated cells were added to the effector: target system at a ratio of 50 : 1. The natural suppressor activity of metrial gland granulated cells did not depend on the amount of metrial gland granulated cells present in a natural killer system. After fractionation in a Percoll gradient, the highest natural killer activity was recorded in a 60% Percoll fraction. The highest and lowest natural suppressor activities were recorded in 30% and 60% Percoll fractions, respectively. The culture medium was characterized by natural suppressor activity as well. The differences in mean areas of metrial gland granulated cells in 30 and 60% Percoll fractions between the pregnant (144.7 ± 13.4 and 75.0 ± 12.5 µm², respectively) and pseudopregnant (97.5 ± 4.9 and 69.2 ± 3.5 µm², respectively) females were reliable. The natural killer activity was estimated in all studied 23 samples of metrial gland granulated cells, among which 18 (79.6 ± 7.8%) displayed the natural suppressor activity as well. The absence of natural suppressor activity in five samples was combined with the absence of this activity in their culture medium and with a reduction in the mean area of metrial gland granulated cells in 30% Percoll fraction to 109 ± 5 µm². The data obtained confirm the known data on a low killer activity of metrial gland granulated cells and demonstrated for the first time the natural suppressor activity of these cells. It was concluded that the natural suppressor activity of metrial gland granulated cells is due to their differentiation from metrial gland granulated cells with natural killer activity.Translated from Ontogenez, Vol. 36, No. 1, 2005, pp. 26–34.Original Russian Text Copyright © 2005 by Podporina, Mikhailov.     

Monosynaptic excitation of facial motoneurons during electrical stimulation of the red nucleus

Synaptic effects of the red nucleus on motoneurons of the facial nucleus were studied in cats. Impulses from the red nucleus activate motoneurons innervating the auricular, buccal, and orbicularis oculi muscles. Monosynaptic EPSPs appeared in all motoneurons which responded to stimulation. Their mean latent period was 1.5±0.04 msec, duration 12.3 ± 0.34 msec, and rise time between 1.5 and 3.2 msec. Repetitive stimulation of the red nucleus led to marked facilitation of the testing EPSP. Facilitation was maximal when the interval between stimuli was 3.5 msec; it was reduced by either a decrease or an increase in the interval. The functional role of the monosynaptic connections of neurons of the red nucleus and of the facial motoneurons is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 4, No. 3, pp. 272–279, May–June, 1972.     

Morphological characteristics of the neuronal population in the feline auditory cortex projecting into the medial geniculate body

The location and morphological profile of auditory cortex neurons projecting to the medial geniculate body were investigated in adult cats using horseradish peroxidase retrograde axonal transport techniques. Sources of descending projections to the medial geniculate body from auditory cortex areas I and II were found to be neurons belonging to deep-lying layers (layer VI and layer V to a lesser extent). By far the majority of corticogeniculate neurons in the auditory cortex were pyramidal cells. In layer VI of the primary auditory area (A1), the number of corticogeniculate neurons reaches 60% of all cells belonging to that layer. The average area (M±m) of the profile of perikarya of corticogeniculate neurons in layer VI, area Al equaled 139.3±2.5 µm² and 219.5±7.0 µm² in layer V neurons; average size of long diameter: 15.0±0.19 and 18.3±0.4 µm respectively. The lower regions of layers III and IV in area Al were found to be the termination point of the greater mass of anterogradely-labeled geniculocortical fibers (terminals of relay neuron axons belonging to the medial geniculate body).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 4, July–August, pp. 513–521, 1989.     

Bicuculline and orientation tuning of neurons of the visual cortex

Orientation tuning (OT) of 68 visual cortex neurons (field 17) was studied in cats under conditions of a GABA-ergic inhibition blockade by microiontophoretic bicuculline applications; the neuronal responses were evoked by flashing light strips. All characteristics of orientational detection in most neurons got worse after the applications. The OT became wider in 76.3% of cases: its mean value increased from 52.7±2.8° to 85.2±4.6°. In 63.6% of cases OT selectivity decreased by one-third, and in 68.5% of neurons the detection quality decreased by 60%, on average. The threshold dose of bicuculline causing the OT extension was injected by the phoretic current of 31.0±4.5 nA, and the optimum effect was reached at 67.1±6.0 nA. The background activity and the response magnitude increased under the bicuculline influence 3.0 and 4.4 times, respectively, compared with the control. A few minutes after the iontophoresis termination, the frequency of neuronal discharges and OT characteristics returned to their initial values. We conclude that the local blocking of intracortical inhibition, which causes disinhibition of afferent inputs from the neighboring cells with different (compared with the recorded cell) preferred orientations, considerably worsens orientational specificity of visual cortex neurons, or even results in a complete loss of such specificity. These data are consistent with the concept that intracortical inhibition plays a leading role in the formation and sharpening of OT in the visual cortex neurons.Neirofiziologiya/Neurophysiology, Vol. 27, No. 1, pp. 54–62, January–February, 1995.     

Properties of the slow excitatory postsynaptic potential in mammalian sympathetic ganglion cells

Two types of slow excitatory postsynaptic potentials (EPSPs) with different properties were found in neurons of the rabbit superior cervical sympathetic ganglion. In our group of neurons slow EPSPs increased during artificial hyperpolarization and decreased during depolarization of the membrane. The input resistance of the cells fell or remained unchanged during the development of slow EPSPs. In the second group of cells slow EPSPs increased during depolarization and decreased during hyperpolarization. The reversal potential of these responses, determined by extrapolation, was –78.9±3.6 mV. Depolarization responses to activation of muscarinic cholinergic receptors by acetylcholine or carbachol developed in 53% of neurons with an increase in input resistance and had a reversal potential of –83.2±6.7 mV. It is suggested that in cells of the first group the ionic mechanism of the slow EPSPs is similar to that of the fast EPSPs, whereas in cells of the second group its main component is a decrease in the potassium conductance of the membrane.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 4, pp. 371–379, July–August, 1981.     

Neuronal responses of a chronically isolated slab of auditory cortex to intracortical stimulation during paroxysmal electrical activity in cats

Responses of 155 neurons 3 weeks after neuronal isolation of a slab of auditory cortex (area AI) to single intracortical stimulating pulses at the level of layer IV were studied in unanesthetized, curarized cats during paroxysmal electrical activity evoked by series of high-frequency (10–20 Hz) electrical stimulation by a current 2–5 times above threshold for the direct cortical response. In response to such stimulation a discharge of paroxysmal electrical activity, lasting from a few seconds to tens of seconds, appeared in the slab. As a rule it consisted of two phases — tonic and clonic. This indicates that cortical neurons can form both phases of paroxysmal cortical activity. Depending on behavior of the neurons during paroxysmal electrical activity and preservation of their ability to respond to intracortical stimulation at this time, all cells tested in the isolated slab were divided into four groups. Their distribution layer by layer and by duration of latent periods was studied. Two-thirds of the neurons tested were shown to generate spike activity during paroxysmal discharges whereas the rest exhibited no such activity. A special role of neurons in layer II in generation of paroxysmal activity in the isolated slab was noted. The view is expressed that at each moment functional neuronal circuits, independent of each other, exist in the slab and also, evidently in the intact cortex, which can interact with one another when conditions change.I. I. Mechnikov Odessa State University. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 3–11, January–February, 1984.     

Self-sustained rhythmic spike and wave activity and response of glial and nerve cells in the cat sensorimotor cortex

During acute experiments on unanesthetized cats, immobilized with myorelaxants, it was found that during rhythmic stimulation (8–14 Hz, duration: 10 sec) of the ventroposterolateral thalamic nucleus brief hyperpolarization is succeeded by depolarization in the pyramidal neurons of the sensorimotor cortex. Following this depolarization, rhythmic (approximately 3 Hz) paroxysmal depolarizing shifts in membrane potential are produced by ending stimulation, succeeded by protracted hyperpolarization and termination of rhythmic wave activity. Depolarization only is observed in glial cells, however, while hyperpolarization sets in after hyperpolarization is completed in the neurons. It is suggested that long-term changes in the membrane potential of cortical cells could make some contribution to the setting up and termination of rhythmic spike and wave activity.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 18, No. 3, pp. 319–325, May–June, 1986.     

Morphological characteristics of callosal neurons of the cat primary auditory cortex (AI)

Cortical stratification of neurons forming callosal projections to the primary cortical area (AI) was investigated in cats using horseradish peroxidase axonal transport techniques. The population of area AI callosal neurons was found to be composed of several groups of cells. The group comprising around 60% of all callosal neurons of this area consists of large layer III pyramidal neurons. Callosal neurons belonging to this layer have a mean perikaryon profile area of 261.8±8.2 µm²; they account for 22% of all cells found in the layer. The second group, comprising 27% of all area AI callosal neurons, was largely made up of large layer V and VI cells; these could not be classed as pyramidal neurons due to the shape of their somata and the geometry of their dendritic arborization. Perikaryon profile in these nonpyramidal neurons occupied an area of 250.3±8.4 µ². No callosal neurons were observed in layer I. These account for 6 and 7% of total numbers of callosal neurons of area AI in layers II and IV. Callosal neurons were found to form projections to all layers of area AI in the contralateral hemisphere. Highest density of callosal fiber endings was observed in layers II and III.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 249–256, March–April, 1990.     

Neuronal responses in the limbic cortex of awake cats during defensive conditioning

Spike activity was investigated in limbic cortex neurons during defensive conditioning to acoustic stimulation in chronic experiments on cats. A relationship was found between the numbers of neurons responding, their contribution to formation of a temporal connection, and the duration of the acoustic stimulus. Phasic responses of 50–500 msec duration with latencies of 15–50 msec were observed for the most part. Intensive spike response with a minimum latency of 15 msec and a duration of between 200 msec and 2.5 sec evolved in most cells (95.1% in field 24 and 83% in field 32) in response to electrical stimulation. Response to acoustic stimulation rose during defensive conditioning in 33.3% cells and declined and finally disappeared in 13.3%, but response at the site where reinforcement was abolished was reproduced in all these cells. It was thus found that the numbers of limbic cortex neurons responding to sound not only fails to increase but actually decreases after training. The limbic cortex is thought to play its most active part in conditioning response to a recognized signal during the period preceding the awaited painful reinforcement.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 5, pp. 660–669, September–October, 1986.     

Synaptic responses of medullary neurons of turtles to stimulation of the locomotor region

Responses of medullary neurons to microstimulation of the locomotor region by a current of up to 30 µA were studied by intracellular recording in turtles. The resting potential recorded in these neurons was from 22 to 42 mV. Depolarization PSPs (EPSPs) were recorded in 43 neurons, hyperpolarization PSPs (IPSPs) in 12, and mixed in 36. Synaptic discharges were observed in 29 neurons. Of these cells 11 generated action potentials without visible PSPs. The latent period of the PSPs was most frequently between 2 and 8 msec. The time from the beginning of the EPSP to the beginning of the action potential was 1–3 msec if the response index was high, but in the case of weaker stimulation, it began to fluctuate strongly and lengthened. Unitary EPSPs were recorded in 15 neurons and IPSPs in three. Their amplitude was 0.6–0.8 mV, from 2 to 12 times less than the depolarization threshold (1–7 mV). These results, together with those obtained previously by extracellular recording of medullary unit activity in turtles and cats, are used to discuss the possible mechanism of spread of locomotor activity.Institute for Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 14, No. 2, pp. 122–129, March–April, 1982.     

Immuno-electron-microscopic study of the prolactin cells in the pituitary gland of male Wistar rats during aging

Summary Prolactin cells were identified by means of immunocytochemistry with protein-A gold as a marker on ultrathin sections of the pituitary gland of young (3–4 months), middle-aged (16–19 months), and aged (26–30 months) male Wistar rats. Point-counting volumetry revealed that the prolactin (PRL) cell-volume density in middle-aged rats was significantly increased in comparison to the volume densities in young and aged rats. Within the PRL-cell population, four types of PRL cells were distinguished on the basis of the shape and size of their secretory granules. During aging, dramatic changes occurred in the relative volumes of the four cell types. The volume percentage of cells with round granules (type I, granule diameter 150–250 nm, and type IIA, granule diameter 250–350 nm) increased from ±30% in young rats to ±90% in old rats. The volume percentage of cells with round and polymorphic granules (type IIB; granule diameter 350–400 nm and type III; granule diameter 500–600 nm) decreased from ±70% in young rats to ±7% in old rats. Age-related changes in serum PRL levels were not found. It is concluded that although during the life span of the male Wistar rat considerable changes in PRL-cell volume densities and in the ratios of PRL-cell types occur serum, PRL levels remain more or less constant.