Tetrodotoxin (TTX; a voltage-sensitive sodium channel blocker) was microinjected bilaterally into the insular (IC), frontal (FC), or parietal (PC) cortex or the ventral caudate nucleus of rats either before or after they were trained in an inhibitory avoidance task. When administered either before or after training, injections of TTX into the IC impaired performance on a 48-hr retention test. INjections of TTX into the PC also impaired retention when administered before training. One week later, rats with cannulae in the IC, FC, and PC received microinjections of TTX either before or after training in a water maze (Morris) spatial learning task and retention was tested 24 hr later. TTX impaired retention when administered to the IC either before or after training. These rindings indicate that a functionally intact IC during and after training in these tasks appears to be essential for the storage of long-term memory.The insular cortex (IC), or visceral neocortex, is known to be involved in visceral reactions and stress (1). The IC receives taste and visceral information from the thalamus (2-4) and sends direct projections to the nucleus of the tractus solitarius (the first-order relay for visceral information) (1). The IC also has connections with limbic structures including the amygdala, the mediodorsal nucleus of the thalamus, and the medial prefrontal cortex (1, 5). Moreover, the IC receives afferent projections from limbic and primary visceral inputs (1, 5). It is well established that the IC is involved in taste/visceral-related memory. Lesions of the IC region in adult rats impair acquisition and retention of conditioned taste aversion (2, 3, 6, 7). Recent findings showing that N-methyl-D-aspartate-induced lesions of the IC disrupt the acquisition of inhibitory avoidance tasks indicated that the IC is also involved in exteronociceptive-based learning (8).In the experiments reported here, tetrodotoxin (TTX; a reversible sodium-channel-dependent activity blocker) (9, 10) was microinjected bilaterally into specific cortical areas to produce reversible inactivation either before or after training in two tasks-inhibitory avoidance and water maze spatial learning. Retention tests were administered .1 or 2 days after training. The findings indicate that TTX microinjected into the IC produces anterograde as well as retrograde memory impairment in both learning tasks.
MATERIALS AND METHODSSurgical,Hitlocal,andhInjectionProcedures.MaleSpragueDawley rats (220-250 g) from Charles River Breeding Laboratories were individually housed and maintained on a 12:12 hr light/dark cycle, with food and water available ad libitum.Behavioral training and testing were conducted during the light portion of the cycle (10:00 a.m. to 2:00 p.m.). One week after arrival, the rats were implanted bilaterally with 15-mm 23-gauge stainless steel cannulae under anesthesia (ketamine hydrochloride, 100 mg/kg i.p., atropine at 0.4 mg/kg; and xylazine at 5.0 mg/kg i.p. as preanesthetics). The tips of the cannulae were aimed 1 mm above the...