The mammalian main olfactory bulb receives a significant noradrenergic input from the locus coeruleus. Norepinephrine is involved in acquisition of conditioned odor preferences in neonatal animals and in some species-specific odor dependent behaviors. Thus far, the role of norepinephrine in odor processing in adult rats remains less studied. We tested the role of noradrenergic modulation in the olfactory bulb of cannulated rats by bilateral injections of vehicle (6 microL saline), the alpha noradrenergic receptor antagonist phentolamine (3.15 or 10 mM), the beta noradrenergic receptor antagonist alprenolol (12 or 120 mM), the alpha1 noradrenergic receptor antagonist prazosin (1 or 10(-2) mM) and the alpha2 noradrenergic receptor antagonist yohimbine (2 or 0.02 mM) 20 min before two different behavioral tasks. We found that local blockade of noradrenergic receptors in the olfactory bulb did not affect the formation of habituation memory to an odorant over sequential presentations separated by 5-min intertrial intervals. However, spontaneous discrimination between chemically related odorants was impaired when noradrenergic receptors, and in particular alpha1 receptors, were blocked by local antagonist infusion into the olfactory bulb. By contrast, discrimination was improved when beta receptors were blocked. These results show that although the formation of a habituation memory to odorants is not affected by noradrenergic modulation, the specificity of this memory is affected. In contrast, reward-motivated discrimination learning was not impaired, but slowed down in rats in which both alpha and beta receptors had been blocked.

Noradrenergic projections from the locus coeruleus (LC) project to the olfactory bulb (OB), a cortical structure implicated in odor learning and perceptual differentiation among similar odorants. We tested the role of OB noradrenaline (NA) in short-term olfactory memory using an animal model of LC degeneration coupled with intrabulbar infusions of NA. Specifically, we lesioned cortical noradrenergic fibers in mice with the noradrenergic neurotoxin N-Ethyl-N-(2-chloroethyl)-2-bromobenzylamine hydrochloride (DSP4) and measured the effects on an olfactory habituation/ spontaneous discrimination task. DSP4-treated mice failed to habituate to repeated odor presentations, indicating that they could not remember odors over the five-minute intertrial interval. We then infused NA bilaterally into the OBs of both DSP4-treated and nonlesioned control animals at two concentrations (10 −3 M and 10 −5 M, 2 ul/side). In DSP4-treated animals, NA administration at either concentration restored normal habituation and spontaneous discrimination performance, indicating that noradrenergic neuromodulation mediates these aspects of perceptual learning and that its efficacy does not require activity-dependent local regulation of NA release. Functional OB learning mechanisms may be necessary for normal odor recognition and differentiation among physically similar odorants.

The perceptual differentiation of odors can be measured behaviorally using generalization gradients. The steepness of these gradients defines a form of olfactory acuity for odor quality that depends on neural circuitry within the olfactory bulb and is regulated by cholinergic activity therein as well as by associative learning. Using this system as a reduced model for age-related cognitive decline, we show that aged mice, while maintaining almost the same baseline behavioral performance as younger mice, are insensitive to the effects of acutely elevated acetylcholine, which sharpens generalization gradients in young adult mice. Moreover, older mice exhibit evidence of chronically elevated acetylcholine levels in the olfactory bulb, suggesting that their insensitivity to further elevated levels of acetylcholine may arise because the maximum capacity of the system to respond to acetylcholine has already been reached. We propose a model in which an underlying, age-related, progressive deficit is mitigated by a compensatory cholinergic feedback loop that acts to retard the behavioral effects of what would otherwise be a substantial age-related decline in olfactory plasticity.We also treated mice with ten-day regimens of olfactory environmental enrichment and/or repeated systemic injections of the acetylcholinesterase inhibitor physostigmine. Each treatment alone sharpened odor quality acuity, but administering both treatments together had no greater effect than either alone. Age was not a significant main effect in this study, suggesting that some capacity for acetylcholine-dependent plasticity is still present in aged mice despite their sharply reduced ability to respond to acute increases in acetylcholine levels.These results suggest a dynamical framework for understanding age-related decline in neural circuit processing in which the direct effects of aging can be mitigated, at least temporarily, by systemic compensatory responses. In particular, a decline in cholinergic efficacy can precede any

Memories are dynamic physical phenomena with psychometric forms as well as characteristic timescales. Most of our understanding of the cellular mechanisms underlying the neurophysiology of memory, however, derives from one-trial learning paradigms that, while powerful, do not fully embody the gradual, representational, and statistical aspects of cumulative learning. The early olfactory system—particularly olfactory bulb—comprises a reasonably well-understood and experimentally accessible neuronal network with intrinsic plasticity that underlies both one-trial (adult aversive, neonatal) and cumulative (adult appetitive) odor learning. These olfactory circuits employ many of the same molecular and structural mechanisms of memory as, for example, hippocampal circuits following inhibitory avoidance conditioning, but the temporal sequences of post-conditioning molecular events are likely to differ owing to the need to incorporate new information from ongoing learning events into the evolving memory trace. Moreover, the shapes of acquired odor representations, and their gradual transformation over the course of cumulative learning, also can be directly measured, adding an additional representational dimension to the traditional metrics of memory strength and persistence. In this review, we describe some established molecular and structural mechanisms of memory with a focus on the timecourses of post-conditioning molecular processes. We describe the properties of odor learning intrinsic to the olfactory bulb and review the utility of the olfactory system of adult rodents as a memory system in which to study the cellular mechanisms of cumulative learning.

This paper presents a CMOS sensor array with a 768 low-noise recording sites for neural recording with 2048 intercalated angle-sensitive pixels for optical read-out. The array is highly scalable because of electrode-level digitization with serial data stream-out. The front-end amplifiers use chopping to reduce flicker noise and achieve an input-referred noise of 4.1µV r ms over a 3.6 kHz bandwidth while occupying an area of only 800µm 2 . Digitization is performed using a distributed ramp ADC that samples every sensor site at 10 kHz. The electrodes have a 50µm pitch and are plated with platinum to increase the interface capacitance and ensure biocompatibility. The sensor array is used to refocus a lenless image and to record neural spiking and local field potentials from a mouse olfactory bulb slice.Index Terms-Action potential, angle-sensitive pixel (ASP), CMOS sensors, local field potential, low-noise amplifiers, microelectrode array (MEA), microelectrodes, neural interface.