The laminar structure and cellular distribution of cytochrome-oxidase (CO) reactivity in supragranular puffs of striate cortex was examined in adult macaque monkeys surviving various periods of monocular enucleation, lid suture, and retinal impulse blockage with tetrodotoxin (TTX). Enucleation and TTX produced a rapid and severe loss in the size of the CO reactive region in puffs dominated by the removed or treated eye compared to slower and less marked reductions obtained in deprived puffs of lid-sutured monkeys. In all deprived animals, the cross-sectional areas of deprived puffs decreased most rapidly in the upper layers (2 and 3A). In long-term enucleated (60 wks) and TTX-treated (4 wks) monkeys, puff area was severely reduced in layer 3B, while reactivity in layer 3B appeared partially spared in lid-sutured monkeys. The density of the CO reaction product was significantly and evenly reduced throughout deprived puffs for all of the monkeys examined; however, this decrease was less severe in adult monkeys lid-sutured for 11 wks. Although no evidence for cell loss was obtained, all three forms of visual deprivation led to lower counts of neuronal perikarya with high levels of CO reaction product in both deprived puff and interpuff areas. This effect was less marked in the deprived puffs of monkeys lid-sutured for 2.5 and 3 yrs, suggesting recovery of CO activity in some neurons. Neurons in deprived puffs and interpuffs were generally similar in size to those in nondeprived regions, although CO-reactive cells were significantly smaller in the deprived puffs of monkeys enucleated for 28.5 or 60 wks. These results indicate that the metabolic response of neuronal elements in supragranular striate cortex depends upon the nature of the visual deficit. The partial sparing of CO reactivity in deprived puffs of lid-sutured monkeys may reflect the continued transmission of certain types of visual stimuli through a closed eyelid.

Unilateral retinal impulse blockage with tetrodotoxin (TTX) induces reversible shrinkage and decreased cytochrome oxidase (CO) activity in alternate rows of supragranular, CO-rich puffs in the adult macaque striate cortex (Wong-Riley & Carroll, 1984b: Carroll & Wong-Riley, 1987). The present study extended the findings to the electron-microscopic (EM) level to determine if various neuropil profiles in control puffs exhibit heterogeneous levels of CO activity, and whether specific processes were more susceptible to intravitreal TTX than others.

Within the neuropil of control puffs, 60% of the total mitochondrial population resided in dendrites, and the majority of dendritic mitochondria were highly reactive for CO. Axon terminals forming symmetrical synapses also contained darkly reactive mitochondria, whereas those forming asymmetrical synapses possessed very few and mainly lightly reactive mitochondria. Unmyelinated axon trunks, myelinated axons, and glia all exhibited low levels of CO activity. Synaptic count revealed a 3:1 ratio of asymmetrical to symmetrical synapses.

Intravitreal TTX for 2–4 weeks adversely affects dendrites and symmetrical terminals much more so than other neuropil processes. There was a general decrease in darkly and moderately reactive mitochondria and an increase in lightly reactive mitochondria throughout the puffs, especially in dendrites. This indicates that afferent blockade is more detrimental to processes of higher metabolic activity. Changes also differed between central and peripheral regions of puffs, and indications of axonal and synaptic reorganization were more evident in the latter. Thus, stabilization of neuronal structure and synapses appears to be activity-dependent even in the adult. A working model of these metabolic and morphological responses to chronic TTX is proposed.

Our previous light-microscopic study indicates that unilateral retinal impulse blockage with tetrodotoxin (TTX) causes a reversible decrease of cytochrome oxidase (CO) in alternating rows of metabolically active zones (puffs) in the adult macaque striate cortex (Wong-Riley & Carroll, 1984b). The goal of the present study was to determine if TTX blockade adversely affects all neurons or only a subpopulation of neurons within the puffs. Three major neuronal types were identified based on mitochondrial CO activities and morphological characteristics. Type A neurons were the most prevalent, consisting of small pyramidal and nonpyramidal neurons that received only symmetrical axosomatic synapses. They had little cytoplasm and relatively low levels of CO activity, and showed the least change with TTX treatment. Type B cells were medium-to-large pyramidal neurons that received exclusively symmetrical axosomatic synapses and were moderately reactive for CO. Impulse blockage caused a decrease in mitochondrial size and packing density, but somal size remained within the control range. Type C cells were medium-sized nonpyramidal neurons contacted by both asymmetrical and symmetrical axosomatic synapses. They contained abundant darkly reactive mitochondria and presumably are metabolically the most active. This cell type suffered the greatest decrease in somal size and packing density of mitochondria, particularly the darkly reactive ones. A rare fourth cell type, type D, was a small, darkly reactive nonpyramidal variety that gave rise to somatodendritic synapses. Their low occurrence prevented statistical analysis under normal and TTX-treated conditions. These data indicate that retinal impulse blockade is most detrimental to the metabolically most active neurons in the adult primate cortical puffs. The alterations are not permanent, because the effects of TTX are fully reversible (Carroll & Wong-Riley, 1987).