Brain Research 888 (2001) 203–211 www.elsevier.com / locate / bres Research report Decreased benzodiazepine receptor density in the cerebellum of early blind human subjects a b a b ´ Sandra M. Sanabria-Bohorquez , Anne G. De Volder , Patricia Arno , Merence Sibomana , b b a, * Ann Coppens , Christian Michel , Claude Veraart a ´ Neural Rehabilitation Engineering Laboratory, GREN-5446, Universite Catholique de Louvain, Avenue Hippocrate, 54, B-1200 Brussels, Belgium b ´ Positron Tomography Laboratory, Universite Catholique de Louvain, Brussels, Belgium Accepted 26 September 2000 Abstract As a first approach to study the effect of early visual deprivation in the GABA-ergic inhibitory system, the distribution of 11 11 benzodiazepine receptors (BZR) was accurately estimated using [ C]flumazenil ([ C]FMZ). Measurements were carried out in five 11 subjects who became blind early in life and in five sighted control subjects. The interactions between [ C]FMZ and BZR were described using a non-linear compartmental analysis which permitted to estimate the BZR synaptic density independently of other model parameters. The distribution of BZR in the visual areas and other cortical regions of blind subjects was qualitatively and quantitatively similar to that of controls. However, the BZR density in the cerebellum was significantly lower in blind than in control subjects ( P,0.01). Our findings suggest that modifications of the cerebellar neural circuitry may be concomitant to the already observed compensatory reorganization in cerebral areas of blind subjects.  2001 Elsevier Science B.V. All rights reserved. Theme: Neurotransmitters, modulators, transporters, and receptors Topic: GABA receptors 11 Keywords: [ C]Flumazenil; Benzodiazepine receptors; Early blindness; Visual cortex; Cerebellum; Plasticity 1. Introduction According to this hypothesis, synaptic contacts would be more numerous and / or hyperactive in EB visual areas Positron emission tomography (PET) studies have [13,58]. Besides, the decreased glucose metabolism level shown that the glucose metabolism in primary and associa- in the EB cerebellum suggests that early visual deprivation tive visual areas of early blind (EB) subjects at rest is may also alter the cerebellar neural organization. comparable to that measured in sighted control (SC) The synaptogenesis process and the later phase of subjects with the eyes open, i.e. to the normally active synaptic elimination observed in primate cerebral cortex visual cortex [58,59]. Brain energy metabolism studies are accompanied by similar changes in several neuro- have demonstrated that the metabolic state of the EB visual transmitter receptor densities (dopaminergic, adrenergic, areas is related to neuronal activity [13]. Furthermore, the serotonergic, cholinergic, and GABAergic receptors) glucose utilization in the cerebellum of EB subjects was [36,37]. Moreover, since the interaction between neuro- significantly lower than in blindfolded SC subjects con- transmitters affects the neuronal cytoarchitecture and corti- trasting the findings in the visual areas [13]. cal developmental processes [17,21,30,31], the combina- The increased metabolism in EB visual cortex has been tion of morphological and neurochemical studies may attributed to the alteration of the phase of synaptic provide further insight on the effects of sensory depriva- elimination following the synaptogenesis process during tion. brain development, due to the lack of visual stimuli [58]. As a first approach to study in vivo the chemical circuitry of the human brain in the case of early blindness, 11 11 we have used [ C]flumazenil ([ C]FMZ) to quantify the *Corresponding author. Tel.: 132-2-764-5446; fax: 132-2-764-9422. E-mail address: veraart@gren.ucl.ac.be (C. Veraart). benzodiazepine (BZ) receptor density of EB and SC 0006-8993 / 01 / $ – see front matter  2001 Elsevier Science B.V. All rights reserved. PII: S0006-8993(00)03049-3