Neurophysiological alterations in caudate neurons in aged cats

doi:10.1016/0006-8993(87)91407-7

Brain Research

Volume 401, Issue 2, 20 January 1987, Pages 213-230

https://doi.org/10.1016/0006-8993(87)91407-7 Get rights and content

Abstract

These neurophysiological studies provide information on the alterations in functional capacity of neurons in the aging caudate nucleus (Cd) of the cat. The major finding is that there is a marked loss of excitation in the Cd during the aging process. This loss is most apparent in animals 11–14 years of age but is demonstrable in animals 6–7 years of age. Extracellular recording techniques were used to test the ability of Cd neurons to respond to activation of two of their major inputs, the precruciate cortex (CX) and the substantia nigra (SN). Types of responses that were evoked in both 1–3- and 11–14-year groups were similar and consisted of excitation, excitation followed by inhibition of action potentials or inhibition alone without preceding excitation. The frequency of occurrence of these responses was altered in the aged animals when either input was stimulated. In 1–3-year-old cats CX stimulation evoked initially excitatory responses in 75% of the cells tested while in 11–14-year-old cats excitatory responses occurred in 62% of the cells. When the SN was stimulated the decrease in initial excitation was greater (69% in 1–3-vs 35% in 11–14-year groups). In all aged animals but not in 1–3-year-old cats stimulation thresholds were higher (39–79%) for evoking excitatory responses than for evoking inhibitory responses. In order to assess synaptic security, the ability of Cd neurons to respond to iterative stimulation was determined. Distributions of the minimum interval necessary to evoke two excitatory responses were constructed. There was a marked increase in the proportion of longer intervals in the aged animals indicating that the synaptic response was less secure. There was a tendency for more of the responses in aged animals to have shorter latencies. This result was probably due to loss secure longer latency responses that are mediated via multisynaptic pathways. These findings indicate that there are functional changes in a population of Cd neurons in aged cats that impair their ability to process information.

References (80)

AbercrombieE.D. et al.
Dopaminergic modulation of sensory response of striatal neurons: single unit studies
Brain Research
(1985)
AdinolfiA.M.
The postnatal development of the caudate nucleus: a Golgi and electron microscopic study of kittens
Brain Research
(1977)
BernardiG. et al.
The action of acetylcholine andl-glutamic acid on rat caudate neurons
Brain Research
(1976)
BuchwaldN.A. et al.
Caudate intracellular responses to thalamic and cortical inputs
Exp. Neurol.
(1973)
BuellS.J. et al.
Quantitative evidence for selective dendritic growth in normal human aging but not in senile dementia
Brain Research
(1981)
ChaseM.H. et al.
Aging of motorneurons and synaptic processes in the cat
Exp. Neurol.
(1985)
CherubiniE. et al.
Caudate neuronal responses evoked by cortical stimulation: contribution of an indirect corticothalamic pathway
Brain Research
(1979)
ConnorJ.R. et al.
Occipital cortical morphology of the rat: alterations with age and environment
Exp. Neurol.
(1980)
DustmanR.E. et al.
The effects of maturation and aging on the waveform of visually evoked potentials
Electroencephalogr. Clin. Neurophysiol.
(1969)
FinchC.E.
Catecholamine metabolism in the brains of aging male mice
Brain Research
(1973)

FisherR.S. et al.

Postnatal ontogeny of evoked neuronal responses in the substantia nigra of the cat

Dev. Brain Res.

(1982)

FloodD.G. et al.

Age-related dendritic growth in dentate gyrus of human brain is followed by regression in the ‘oldest old’

Brain Research

(1985)

GovoniS. et al.

Dopamine receptor sensitivity in brain and retina of rats during aging

Brain Research

(1977)

HarrisonJ. et al.

Auditory brainstem response in the aged cat

Neurobiol. Aging

(1982)

HornykiewiczO.

Commentary: Parkinson's disease and its chemotherapy

Biochem. Pharmacol.

(1975)

HullC.D. et al.

Intracellular response of caudate neurons to temporally and spatially combined stimuli

Exp. Neurol.

(1973)

HullC.D. et al.

Quantitative developmental studies of feline neostriatal spiny neurons

Dev. Brain Res.

(1981)

JonecV.J. et al.

Senescence and dopamine uptake by subcellular fractions of the C57BL/6J male mouse brain

Brain Research

(1975)

JonesR.S.G. et al.

Altered sensitivity of forebrain neurons to iontophoretically applied noradrenaline in aging rats

Neurobiol. Aging

(1983)

KitaiS.T. et al.

Monosynaptic inputs to caudate neurons identified by intracellular injection of horseradish peroxidase

Brain Research

(1976)

LandfieldP.W. et al.

Impaired synaptic potentiation processes in the hippocampus of aged memory-deficient rats

Brain Research

(1978)

LandfieldP.W. et al.

Quantification of synaptic vesicles in hippocampus of aging rat and initial studies of possible relations to neurophysiology

Brain Res. Bull.

(1979)

LevineM.S. et al.

Quantitative morphology of medium-sized caudate spiny neurons in aged cats

Neurobiol. Aging

(1986)

LevineM.S. et al.

Development of spontaneous neuronal activity in the caudate nucleus, globus pallidus-entopeduncular nucleus, and substania nigra of the cat

Dev. Brain Res.

(1982)

LevineM.S. et al.

Postnatal development of identified medium-sized caudate spiny neurons in the cat

Dev. Brain Res.

(1986)

LevineM.S. et al.

Effects of caudate nucleus or frontal cortical ablations in kittens: motor activity and visual discrimination performance in neonatal and juvenile kittens

Exp. Neurol.

(1978)

LidskyT.I. et al.

A neurophysiological analysis of the development of cortico-caudate connections in the cat

Exp. Neurol.

(1976)

LighthallJ.W. et al.

A short duration GABAergic inhibition in identified neostriatal medium spiny neurons: in vitro slice study

Brain Res. Bull.

(1983)

MarwahaJ. et al.

Changes in noradrenergic neurotransmission in rat cerebellum during aging

Neurobiol. Aging

(1981)

McGeerE.G. et al.

Aging and brain enzymes

Exp. Gerontol.

(1971)

MercuriN. et al.

Dopamine decreases cell excitability in rat striatal neurons by pre- and postsynaptic mechanism

Brain Research

(1985)

MorrisR. et al.

Intracellular analysis of the development of responses of caudate neurons to stimulation of cortex, thalamus and substantia nigra in the kitten

Brain Research

(1979)

OlmsteadC.E. et al.

Effects of caudate nucleus or frontal cortical ablation in cats. IV. Bar pressing and maze learning performance

Exp. Neurol.

(1976)

OlpeH.R. et al.

Age-related decline in the activity of noradrenergic neurons in the rat locus coeruleus

Brain Research

(1982)

RogersJ. et al.

Senescent changes in a neurobiological model system: cerebellar Purkinje cell electrophysiology and correlative anatomy

Neurobiol. Aging

(1980)

RogersJ. et al.

Senescent pathology of cerebellum: Purkinje neurons and their parallel fiber afferents

Neurobiol. Aging

(1981)

RutledgeL.T. et al.

Morphological changes in pyramidal cells of mammalian neocortex associated with increased use

Exp. Neurol.

(1974)

SabelB.A. et al.

Extensive loss of subcortical neurons in the aging rat brain

Exp. Neurol.

(1981)

SchadeJ.P. et al.

Changes during growth in the volume and surface area of cortical neurons in the rabbit

Exp. Neurol.

(1960)

ScheibelM.E. et al.

Progressive dendritic changes in aging human cortex

Exp. Neurol.

(1975)

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Neurophysiological alterations in caudate neurons in aged cats

Abstract

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