Behavioural Brain Research 89 (1997) 61 – 70 Research report Recovery of function is associated with increased spine density in cortical pyramidal cells after frontal lesions and/or noradrenaline depletion in neonatal rats Bryan Kolb a, *, Jane Stewart b , Robert J. Sutherland c a Department of Psychology, Uniersity of Lethbridge, Lethbridge, AB, T1K 3M4, Canada b Concordia Uniersity, Montreal, Canada c Uniersity of New Mexico, Albuquerque, NM, USA Received 21 September 1996; received in revised form 3 March 1997; accepted 3 March 1997 Abstract Rats were given medial frontal lesions at 7 days of age and were tested as adults on tests of forelimb use, forelimb tactile sensitivity, tongue use, hindleg use, and in a spatial navigation task. The brains were processed with a modified Golgi-Cox procedure and dendritic arborization and spine density was measured. The animals showed recovery only on the spatial task and this was associated with an increase in the number of spines per unit length of dendrite. We also reanalyzed Golgi-Cox stained material from an experiment in which animals were depleted of cortical noradrenaline (NA) in infancy and then given frontal lesions on day 7. The NA depletion blocked the recovery from frontal lesions. Analysis of dendritic morphology showed that in otherwise intact rats, NA depletion decreased dendritic arbor but increased spine density to the level of frontal operates. Depleted frontal-operates showed no additional increase in spine density and also showed a decrease in dendritic arborization. These results suggest that recovery from neonatal cortical injury and from neonatal noradrenaline depletion may be supported by changes in both the dendritic arborization and the spine density in the remaining cortex. © 1997 Elsevier Science B.V. Keywords: Frontal cortex; Recovery of function; Dendritic branching; Spine density; Prefrontal; Dendrite; Spine; Recovery; Noradrenaline 1. Introduction There is now an extensive literature showing that the effects of frontal cortical injury in both rats and cats varies with precise age at injury and the nature of the behavioural tests employed [12,33]. For example, we have shown that rats with large frontal removals on days 1–5 are severely impaired in adulthood on various behavioural tasks whereas rats with similar removals on days 7–12 are much less impaired, if at all [10,23,24]. Injuries later in development, such as around weaning, again lead to significant behavioural disturbances [22]. It is likely that the consistent recovery observed in rats with extensive frontal lesions on days 7–10 is associ- ated with some type of cerebral reorganization that allows the animals to literally do ‘more with less’. Our initial attempts to identify the nature of this reorganization focused upon studies of cortical connec- tivity and dendritic organization [15,17]. In these exper- iments we found that when the frontal cortex was removed around 10 days of age there was a subsequent increase in dendritic arborization throughout the re- maining neocortex. This increase in arborization was associated with recovery of performance of various neuropsychological tests but rather poor recovery of * Corresponding author. Tel.: +1 403 3292405, fax: +1 403 3292555, e-mail: Kolb@HG.ULETH.CA 0166-4328/97/$17.00 © 1997 Elsevier Science B.V. All rights reserved. PII S0166-4328(97)00058-2