MOLECULAR, CELLULAR, AND NEUROANATOMICAL SUBSTRATES OF PLACE LEARNING

Learning and remembering the location of food resources, predators, es cape routes, and immediate kin is perhaps the most essential form of h igher cognitive processing in mammals. Two of the most frequently stud ied forms of place learning are spatial learning and contextual condit ioning. Spatial learning refers to an animal's capacity to learn the l ocation of a reward, such as the escape platform in a water maze, whil e contextual conditioning taps into an animal's ability to associate s pecific places with aversive stimuli, such as an electric shock. Recen tly, transgenic and gene targeting techniques have been introduced to the study of place learning. In contrast with the abundant Literature on the neuroanatomical substrates of place learning in rats, very Litt le has been done in mice. Thus, in the first part of this article, we will review our studies on the involvement of the hippocampus in both spatial learning and contextual conditioning. Having demonstrated the importance of the hippocampus to place learning, we will then focus at tention on the molecular and cellular substrates of place learning. We will show that just as in rats, mouse hippocampal pyramidal cells can show place specific firing. Then, we mill review our evidence that hi ppocampal-dependent place learning involves a number of interacting ph ysiological mechanisms with distinct functions. We will show that in a ddition to long-term potentiation, the hippocampus uses a number of ot her mechanisms, such as short-term-plasticity and changes in spiking, to process, store, and recall information. Much of the focus of this a rticle is on genetic studies of learning and memory (L&M). However, th ere is no single experiment that can unambiguously connect any cellula r or molecular mechanism with L&M. Instead, several different types of studies are required to determine whether any one mechanism is involv ed in L&M, including (i) the development of biologically based learnin g models that explain the involvement of a given mechanism in L&M, (ii ) lesion experiments (genetics and pharmacology), (iii) direct observa tions during learning, and (iv) experiments where learning is triggere d by turning on the candidate mechanism. We will show how genetic tech niques will be key to unraveling the molecular and cellular basis of p lace learning. (C) 1998 Academic Press.