Tobacco use is a major health problem that is estimated to cause 4 million deaths a year worldwide. Nicotine is the main addictive component of tobacco. It acts as an agonist to activate and desensitize nicotinic acetylcholine receptors (nAChRs). A component of nicotine's addictive power is attributable to actions on the mesolimbic dopaminergic…

The present studies explored the role of the medial striatum in learning when task contingencies change. Experiment 1 examined whether the medial striatum is involved in place reversal learning. Testing occurred in a modified cross-maze across two consecutive sessions. Injections of the local anesthetic, bupivacaine, into the medial striatum, did…

Two experiments examined the effects of reductions in cortical cholinergic function on performance of a novel task that allowed for the simultaneous assessment of attention to a visual stimulus and memory for that stimulus over a variable delay within the same test session. In the first experiment, infusions of the muscarinic receptor antagonist…

The relevance of perirhinal cortical cholinergic and glutamatergic neurotransmission for taste recognition memory and learned taste aversion was assessed by microinfusions of muscarinic (scopolamine), NMDA (AP-5), and AMPA (NBQX) receptor antagonists. Infusions of scopolamine, but not AP5 or NBQX, prevented the consolidation of taste recognition…

We investigated the role of acetylcholine (ACh) during encoding and retrieval of tone/shock-induced fear conditioning with the aim of testing Hasselmo's cholinergic modulation model of encoding and retrieval using a task sensitive to hippocampal disruption. Lesions of the hippocampus impair acquisition and retention of contextual conditioning with…

A recent study suggests that lesions to all major areas of the cholinergic basal forebrain in the rat (medial septum, horizontal limb of the diagonal band of Broca, and nucleus basalis magnocellularis) impair a spatial working memory task. However, this experiment used a surgical technique that may have damaged cerebellar Purkinje cells. The…

Cholinergic systems are critical to the neural mechanisms mediating learning. Reduced nicotinic cholinergic receptor (nAChR) binding is a hallmark of normal aging. These reductions are markedly more severe in some dementias, such as Alzheimer's disease. Pharmacological central nervous system therapies are a means to ameliorate the cognitive…

Previous work has demonstrated that drugs increasing brain concentrations of acetylcholine can enhance cognition in aging and brain-damaged organisms. The present study assessed whether galantamine (GAL), an allosteric modulator of nicotinic cholinergic receptors and weak acetylcholinesterase inhibitor, could improve acquisition and retention of…

Motor learning is a very basic, essential form of learning that appears to share common mechanisms across different motor systems. We evaluate and compare a few conceptual models for learning in a relatively simple neural system, the vestibulo-ocular reflex (VOR) of vertebrates. We also compare the different animal models that have been used to…

Stressful life events can have profound effects on our cognitive and motor abilities, from those that could be construed as adaptive to those not so. In this review, I discuss the general notion that acute stressful experience necessarily impairs our abilities to learn and remember. The effects of stress on operant conditioning, that is, learned…

In a previous functional magnetic resonance imaging (fMRI) study we demonstrated an involvement of the medial temporal lobe (MTL) during an implicit learning task. We concluded that the MTL was engaged because of the complex contingencies that were implicitly learned. In addition, the basal ganglia demonstrated effects of a paralleled…

Rats were trained to search for a food reward hidden under sawdust in the center of a square-shaped enclosure designed to force orientation on the basis of the overall geometry of the environment. They were then tested in a number of enclosures differing in shape and in size (rectangular-, double-side square-, and equilateral triangle-shaped…

We investigated learning-related changes in amplitude, scalp topography, and source localization of the mismatch negativity (MMN), a neurophysiological response correlated with auditory discrimination ability. Participants (n = 32) underwent two EEG recordings while they watched silent films and ignored auditory stimuli. Stimuli were a standard…

Brain-derived neurotrophic factor (BDNF) is a potent modulator of synaptic transmission and plasticity in the CNS, acting both pre- and postsynaptically. We demonstrated recently that BDNF/TrkB signaling increases dendritic spine density in hippocampal CA1 pyramidal neurons. Here, we tested whether activation of the prominent ERK (MAPK) signaling…

Extinction of classically conditioned fear, like its acquisition, is active learning, but little is known about its molecular mechanisms. We recently reported that temporal massing of conditional stimulus (CS) presentations improves extinction memory acquisition, and suggested that temporal spacing was less effective because individual CS…