Skip to main content
Log in

Changes in the total number of dentate granule cells in juvenile and adult rats: A correlated volumetric and 3H-thymidine autoradiographic study

  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Summary

The total number of granule cells in the dentate gyrus was estimated in 17 male rats, four each aged 30, 120, and 200 days, and five aged 365 days. There is a substantial 35–43% linear increase between 1 month and 1 year. Two parameters of the granular layer are involved in the numerical change. First, total granular layer volume grows linearly with age. Second, average volume of a single granule cell nucleus in the ventral dentate gyrus decreases with age. Older rats tend to have a larger granular layer filled with more and smaller cells. In another group of 21 male rats, 3H-thymidine injections were given on four consecutive days during juvenile (30–33, n = 6) and adult life (60–63, n = 5; 120–123, n = 6; 180–183, n = 4). All animals survived to 200 days of age. The proportion of labeled mature granule cells and labeled presumptive granule cell precursors were determined in anatomically-matched slices. With older ages at injection, there is a decline in labeled mature granule cells and a concurrent increase in labeled precursors. These data are compatible with the constant level of granule cell increase determined volumetrically. Most of the late granule cells originate nearly simultaneously along the base of the main bulk of the granular layer; very few are found in the dorsal tip (septal extreme) and ventral tip (temporal extreme). This study is the first demonstration of a net numerical gain in a neuronal population during adulthood in the mammalian brain. Since the granule cells play a pivotal role in hippocampal function, these data suggest that their influence grows with age.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abercrombie M (1946) Estimation of nuclear population from microtome sections. Anat Rec 94: 239–247

    Article  PubMed  CAS  Google Scholar 

  • Altman J (1963) Autoradiographic study of cell proliferation in the brians of rats and cats. Anat Rec 145: 573–592

    Article  PubMed  CAS  Google Scholar 

  • Altman J (1969a) Autoradiographic and histological studies of postnatal neurogenesis. III. Dating the time of production and onset of differentiation of cerebellar microneurons in rats. J Comp Neurol 136: 269–294

    Article  PubMed  CAS  Google Scholar 

  • Altman J (1969b) Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol 137: 433–458

    Article  PubMed  CAS  Google Scholar 

  • Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124: 319–336

    Article  PubMed  CAS  Google Scholar 

  • Altman J, Das GD (1966) Autoradiographic and histological studies of postnatal neurogenesis. I. A longitudinal investigation of the kinetics, migration and transformation of cells incorporating tritiated thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions. J Comp Neurol 126: 337–390

    Article  PubMed  CAS  Google Scholar 

  • Altman J, Brunner R, Bayer SA (1973) The hippocampus and behavioral maturation. Behav Biol 8: 557–596

    Article  PubMed  CAS  Google Scholar 

  • Barnes D, Altman J (1973) Effects of two levels of gestational-lactational undernutrition on the postweaning growth of the rat cerebellum. Exp Neurol 38: 420–428

    Article  PubMed  CAS  Google Scholar 

  • Bayer SA (1976) Ontogeny of the hippocampal region in the rat. Paper presented at the Neurosciences Research Program Work Session on The Hippocampal Formation: Structure and Function. Woods Hole, MA, May 11–14, 1976

  • Bayer SA (1980) The development of the hippocampal region in the rat. I. Neurogenesis examined with 3H-thymidine autoradiography. J Comp Neurol 190: 87–114

    Article  PubMed  CAS  Google Scholar 

  • Bayer SA, Altman J (1974) Hippocampal development in the rat: Cytogenesis and morphogenesis examined with autoradiography and low-level X-irradiation. J Comp Neurol 158: 55–80

    Article  PubMed  CAS  Google Scholar 

  • Bayer SA, Altman J (1975) Radiation-induced interference with postnatal hippocampal cytogenesis in rats and its long-term effects on the acquisition of neurons and glia. J Comp Neurol 163: 1–20

    Article  Google Scholar 

  • Bayer SA, Brunner RL, Hine R, Altman I (1973) Behavioural effects of interference with the postnatal acquisition of hippocampal granule cells. Nature 242: 222–224

    CAS  Google Scholar 

  • Conover WJ (1971) Practical nonparametric statistics. Wiley, New York

    Google Scholar 

  • Douglas RJ (1967) The hippocampus and behavior. Psychol Bull 67: 416–422

    Article  PubMed  CAS  Google Scholar 

  • Douglas RJ (1975) The development of hippocampal function: Implications for theory and therapy. In: Isaacson RL, Pribram KH (eds) The hippocampus: Neurophysiology and behavior, vol 2. Plenum Press, New York, pp 327–361

    Google Scholar 

  • Douglas RJ, Pribram KH (1966) Learning and limbic lesions. Neuropsychologia 4: 197–220

    Article  Google Scholar 

  • Elias H, Hennig A, Schwartz DE (1971) Stereology. Applications to biomedical research. Phys Rev 51: 158–200

    CAS  Google Scholar 

  • Gaarskjaer FB (1978) Organization of the mossy fiber system of the rat studied in extended hippocampi. I. Terminal area related to number of granule and pyramidal cells. J Comp Neurol 178: 49–72

    Article  PubMed  CAS  Google Scholar 

  • Gazzara RA, Altman J (1981) Early postnatal X-irradiation of the hippocampus and discrimination learning in adult rats. J Comp Physiol Psychol 95: 484–495

    Article  PubMed  CAS  Google Scholar 

  • Hendry IA (1976) A method to correct adequately for the change in neuronal size when estimating neuronal numbers after nerve growth factor treatment. J Neurocytol 5: 337–349

    Article  PubMed  CAS  Google Scholar 

  • Hirsch R (1974) The hippocampus and contextual retrieval of information from memory. Behav Biol 12: 421–444

    Article  Google Scholar 

  • Kaplan MS, Hinds JW (1977) Neurogenesis in the adult rat: Electron microscopic analysis of light radioautographs. Science 197: 1092–1094

    Article  PubMed  CAS  Google Scholar 

  • Kapp BS, Gallagher M, Holmquist BK, Theall CL (1978) Retrograde amnesia and hippocampal stimulation: Dependence upon the nature of associations formed during conditioning. Behav Biol 24: 1–23

    Article  PubMed  CAS  Google Scholar 

  • McCleary RA (1966) Response-Modulation functions of the limbic system: Initiation and suppression. In: Stellar E, Sprague JN (eds) Progress in physiological psychology. Academic Press, New York, pp 209–272

    Google Scholar 

  • Nicholson JL, Altman J (1972) The effects of early hypo- and hyperthyroidism on the development of rat cerebellar cortex. I. Cell proliferation and differentiation. Brain Res 44: 13–23

    Article  PubMed  CAS  Google Scholar 

  • O'Keefe J, Nadel L (1978) The hippocampus as a cognitive map. Clarendon Press, Oxford, England

    Google Scholar 

  • Olton DS (1978) The function of septo-hippocampal connections in spatially organized behavior. In: Functions of the septohippocampal system. CIBA Foundation Symposium 58. Elsevier, Amsterdam, pp 327–342

    Google Scholar 

  • Puri PS, Yackel JW (1981) Statistical estimation of the number of spherical bodies embedded in a three-dimensional medium. Dept. of Statistics, Mimeo Series, Purdue University, West Lafayette, IN, USA

    Google Scholar 

  • Roselli-Austin L, Altman J (1979) The postnatal development of the main olfactory bulb of the rat. J Dev Physiol 1: 295–313

    Google Scholar 

  • Schlessinger AR, Cowan WM, Gottlieb DI (1975) An autoradiographic study of the time of origin and the pattern of granule cell migration in the dentate gyrus of the rat. J Comp Neurol 159: 149–176

    Article  PubMed  CAS  Google Scholar 

  • Scoville W, Milner B (1957) Loss of recent memory after bilaterial hippocampal lesions. J Neurol Neurosurg Psychiatry 20: 11–21

    Article  PubMed  CAS  Google Scholar 

  • Weibel ER (1969) Stereological principles of mophometry in electron microscopic cytology. Int Rev Cytol 26: 235–302

    Article  PubMed  CAS  Google Scholar 

  • West MJ, Andersen AH (1980) An allometric study of the area dentata in the rat and mouse. Brain Res Rev 2: 317–348

    Article  CAS  Google Scholar 

  • Wimer RE, Wimer CC, Vaughn JE, Barber RP, Balvanz BA, Chernow C (1978) The genetic organization of neuron number in the granule cell layer of the area dentata in house mice. Brain Res 157: 105–122

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by the National Science Foundation (Grant No. BNS 79-21303)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bayer, S.A. Changes in the total number of dentate granule cells in juvenile and adult rats: A correlated volumetric and 3H-thymidine autoradiographic study. Exp Brain Res 46, 315–323 (1982). https://doi.org/10.1007/BF00238626

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00238626

Key words

Navigation