Hippocampal Modulation of Recognition, Conditioning, Timing, and Space: Why So Many Functions?

Advanced Research Projects Agency (ONR N00014-92-J-4015); National Science Foundation (IRI-90-24877); Office of Naval Research (N00014-91-J-1309

Dorsal-CA1 hippocampal neuronal ensembles encode nicotine-reward contextual associations

Natural and drug rewards increase the motivational valence of stimuli in the environment that, through Pavlovian learning mechanisms, become conditioned stimuli that directly motivate behavior in the absence of the original unconditioned stimulus. While the hippocampus has received extensive attention for its role in learning and memory processes, less is known regarding its role in drug-reward associations. We used in vivo Ca2+ imaging in freely moving mice during the formation of nicotine preference behavior to examine the role of the dorsal-CA1 region of the hippocampus in encoding contextual reward-seeking behavior. We show the development of specific neuronal ensembles whose activity encodes nicotine-reward contextual memories and that are necessary for the expression of place preference. Our findings increase our understanding of CA1 hippocampal function in general and as it relates to reward processing by identifying a critical role for CA1 neuronal ensembles in nicotine place preference

The hippocampus and cerebellum in adaptively timed learning, recognition, and movement

The concepts of declarative memory and procedural memory have been used to distinguish two basic types of learning. A neural network model suggests how such memory processes work together as recognition learning, reinforcement learning, and sensory-motor learning take place during adaptive behaviors. To coordinate these processes, the hippocampal formation and cerebellum each contain circuits that learn to adaptively time their outputs. Within the model, hippocampal timing helps to maintain attention on motivationally salient goal objects during variable task-related delays, and cerebellar timing controls the release of conditioned responses. This property is part of the model's description of how cognitive-emotional interactions focus attention on motivationally valued cues, and how this process breaks down due to hippocampal ablation. The model suggests that the hippocampal mechanisms that help to rapidly draw attention to salient cues could prematurely release motor commands were not the release of these commands adaptively timed by the cerebellum. The model hippocampal system modulates cortical recognition learning without actually encoding the representational information that the cortex encodes. These properties avoid the difficulties faced by several models that propose a direct hippocampal role in recognition learning. Learning within the model hippocampal system controls adaptive timing and spatial orientation. Model properties hereby clarify how hippocampal ablations cause amnesic symptoms and difficulties with tasks which combine task delays, novelty detection, and attention towards goal objects amid distractions. When these model recognition, reinforcement, sensory-motor, and timing processes work together, they suggest how the brain can accomplish conditioning of multiple sensory events to delayed rewards, as during serial compound conditioning.Air Force Office of Scientific Research (F49620-92-J-0225, F49620-86-C-0037, 90-0128); Advanced Research Projects Agency (ONR N00014-92-J-4015); Office of Naval Research (N00014-91-J-4100, N00014-92-J-1309, N00014-92-J-1904); National Institute of Mental Health (MH-42900

A neural network model of adaptively timed reinforcement learning and hippocampal dynamics

A neural model is described of how adaptively timed reinforcement learning occurs. The adaptive timing circuit is suggested to exist in the hippocampus, and to involve convergence of dentate granule cells on CA3 pyramidal cells, and NMDA receptors. This circuit forms part of a model neural system for the coordinated control of recognition learning, reinforcement learning, and motor learning, whose properties clarify how an animal can learn to acquire a delayed reward. Behavioral and neural data are summarized in support of each processing stage of the system. The relevant anatomical sites are in thalamus, neocortex, hippocampus, hypothalamus, amygdala, and cerebellum. Cerebellar influences on motor learning are distinguished from hippocampal influences on adaptive timing of reinforcement learning. The model simulates how damage to the hippocampal formation disrupts adaptive timing, eliminates attentional blocking, and causes symptoms of medial temporal amnesia. It suggests how normal acquisition of subcortical emotional conditioning can occur after cortical ablation, even though extinction of emotional conditioning is retarded by cortical ablation. The model simulates how increasing the duration of an unconditioned stimulus increases the amplitude of emotional conditioning, but does not change adaptive timing; and how an increase in the intensity of a conditioned stimulus "speeds up the clock", but an increase in the intensity of an unconditioned stimulus does not. Computer simulations of the model fit parametric conditioning data, including a Weber law property and an inverted U property. Both primary and secondary adaptively timed conditioning are simulated, as are data concerning conditioning using multiple interstimulus intervals (ISIs), gradually or abruptly changing ISis, partial reinforcement, and multiple stimuli that lead to time-averaging of responses. Neurobiologically testable predictions are made to facilitate further tests of the model.Air Force Office of Scientific Research (90-0175, 90-0128); Defense Advanced Research Projects Agency (90-0083); National Science Foundation (IRI-87-16960); Office of Naval Research (N00014-91-J-4100

Neural Dynamics of Autistic Behaviors: Cognitive, Emotional, and Timing Substrates

What brain mechanisms underlie autism and how do they give rise to autistic behavioral symptoms? This article describes a neural model, called the iSTART model, which proposes how cognitive, emotional, timing, and motor processes may interact together to create and perpetuate autistic symptoms. These model processes were originally developed to explain data concerning how the brain controls normal behaviors. The iSTART model shows how autistic behavioral symptoms may arise from prescribed breakdowns in these brain processes.Air Force Office of Scientific Research (F49620-01-1-0397); Office of Naval Research (N00014-01-1-0624