Anterior communicating artery (ACoA) aneurysm rupture can lead to an anterograde amnesia syndrome similar to that observed after damage to the hippocampus and medial temporal lobes (MT). It is currently believed that ACoA amnesia results from basal forebrain damage that disrupts hippocampal processing without direct hippocampal damage. Converging evidence from animal studies and computational modeling suggests that qualitative differences may exist in the pattern of memory impairment after basal forebrain or MT damage. For example, animals with basal forebrain but not hippocampal damage are impaired at delay eyeblink classical conditioning (EBCC). In this study, individuals with ACoA amnesia were shown to be impaired at delay EBCC compared with matched controls; this contrasts with the spared delay EBCC previously observed in MT amnesia. This finding suggests the beginning of a possible dissociation between the memory impairments in MT versus ACoA amnesia.

Previously we have shown that Gluck and Myers's (1993) corticohippocampal
model could be extended to incorporate Hasselmo and Schnell's (1994) hypothesis that
septohippocampal cholinergic processes regulate the amount of information storage in
hippocampus. The generalized model could account for the effect of the anticholinergic drug
scopolamine in delaying onset of eyeblink conditioning (Myers et al., 1996). Here, we show
that the model also accounts for additional eyeblink results, including quick recovery after

In previous papers we have investigated the functional role of the hippocampal region in learning and memory using connectionist modeling techniques to focus on behavioral processes involved in associative learning (Gluck & Myers, 1993; Myers & Gluck,
1994). Additional work has extended the model by using known neuroanatomical architecture of the hippocampal formation to ascribe specific hippocampal and entorhinal cortical functions (Myers, Gluck & Granger, 1995)

Although most analyses of amnesia have focused on the loss of explicit declarative and episodic memories following hippocampal-region damage, considerable insights into amnesia can also be realised by studying hippocampal function in simple procedural, or habit-based, associative learning tasks. Although many simple forms of associative learning are unimpaired by hippocampal damage, more complex tasks which require sensitivity to unreinforced stimuli, configurations of multiple stimuli, or contextual information are impaired by hippocampal damage. In several recent papers we have developed a computational theory of hippocampal function which argues that this brain region plays a critical role in the formation of new stimulus representations during learning (Gluck & Myers, 1993, 1995; Myers & Gluck, 1996; Myers, Gluck, & Granger, 1995). We have applied this theory to a broad range of empirical data from studies of classical conditioning in both intact and hippocampal-lesioned animals, and the model correctly accounts for these data. The classical conditioning paradigm can be adapted for use in humans, and similar results for acquisition are obtained in both normal and hippocampal-damaged humans. More recently, we have begun to address an important set of category learning studies in both normals and hippocampal-damaged amnesics. This work integrates experimental studies of amnesic category learning (Knowlton, Squire, & Gluck, 1994) with theoretical accounts of associative learning, and builds on previously established behavioural correspondences between animal conditioning and human category learning (Gluck & Bower, 1988a). Our work to date illustrates some initial progress towards a more integrative understanding of hippocampal function in both animal and human learning, which may be useful in guiding further empirical and theoretical research in human memory and amnesia.

A previous neurocomputational model of corticohippocampal interaction (Gluck & Myers, 1993) can provide a framework for examining the behavioral effects of septohippocampal modulation during classical conditioning. The model assumes that the hippocampal region is necessary for forming new stimulus representations during learning, but not for the formation of simple associations. This paper considers how septohippocampal interaction could affect this function. The septal nuclei provide several modulatory inputs to the hippocampus, including a cholinergic input which Hasselmo (1995) has suggested may function to regulate hippocampal dynamics on a continuum between two states: a storage state in which incoming information is encoded as an intermediate-term memory and a recall state when this information is reactivated. In this theory, anticholinergic drugs such as scopolamine should disrupt learning by selectively reducing the hippocampus's ability to store new information. An approximation of Hasselmo's idea can be implemented in the corticohippocampal model by a simple manipulation of hippocampal learning rate; this manipulation is formally equivalent to adjusting the amount of time the hippocampus spends in learning and recall states. With this manipulation, the model successfully accounts for the effects of scopolamine in retarding classical conditioning in humans (Solomon, Groccia-Ellison, Flynn, Mirak, Edwards, Dunehew, & Stanton, 1993) and animals (Solomon, Soloman, van der Schaaf, & Perry, 1983). The model further predicts that although cholinergic agonists (such as Tacrine) may improve learning in subjects with artificially depressed brain acetylcholine levels, there may be limited memory improvement in normal subjects from such cholinergic therapy. This is consistent with the general finding of a U-shaped dose response curve for cholinergic drugs in normal subjects: low to moderate doses may improve learning, but higher doses are ineffective or even degrade learning (e.g., Ennaceur & Meliani, 1992; Dumery, Derer, & Blozovski, 1988; etc.).

Calcium channel antagonists of the dihydropyridine class have been widely used in the treatment of cardiovascular diseases such as hypertension and angina because of their ability to relax blood vessels and inhibit cardiac contractions (Fleckenstein, 1977). These effects are achieved principally by inhibiting entry of calcium into cells through blockade of voltage-dependent L channels (Hoffman, Nastainczyk, Rohrsten, Schneider, & Sieber, 1987). Because calcium channel antagonists are powerful vasodilators, they have also ...