Differential effects and rates of normal aging in cerebellum and hippocampus.

Cognitive functions show many alternative outcomes and great individual variation during normal aging. We examined learning over the adult life span in CBA mice, along with morphological and electrophysiological substrates. Our aim was to compare cerebellum-dependent delay eyeblink classical conditioning and hippocampus-dependent contextual fear conditioning in the same animals using the same conditioned and unconditioned stimuli for eyeblink and fear conditioning. In a subset of the behaviorally tested mice, we used unbiased stereology to estimate the total number of Purkinje neurons in cerebellar cortex and pyramidal neurons in the hippocampus. Several forms of synaptic plasticity were assessed at different ages in CBA mice: long-term depression (LTD) in both cerebellum and hippocampus and NMDA-mediated long-term potentiation (LTP) and voltage-dependent calcium channel LTP in hippocampus. Forty-four CBA mice tested at one of five ages (4, 8, 12, 18, or 24 months) demonstrated statistically significant age differences in cerebellum-dependent delay eyeblink conditioning, with 24-month mice showing impairment in comparison with younger mice. These same CBA mice showed no significant differences in contextual or cued fear conditioning. Stereology indicated significant loss of Purkinje neurons in the 18- and 24-month groups, whereas pyramidal neuron numbers were stable across age. Slice electrophysiology recorded from an additional 48 CBA mice indicated significant deficits in LTD appearing in cerebellum between 4 and 8 months, whereas 4- to 12-month mice demonstrated similar hippocampal LTD and LTP values. Our results demonstrate that processes of aging impact brain structures and associated behaviors differentially, with cerebellum showing earlier senescence than hippocampus.

Flexibility in action: Development of locomotion under overhead barriers.

Behavioral flexibility-the ability to tailor motor actions to changing body-environment relations-is critical for functional movement. Navigating the everyday environment requires the ability to generate a wide repertoire of actions, select the appropriate action for the current situation, and implement it quickly and accurately. We used a new, adjustable barrier paradigm to assess flexibility of motor actions in 20 17-month-old (eight girls, 12 boys) and 14 13-month-old (seven girls, eight boys) walking infants and a comparative sample of 14 adults (eight women, six men). Most participants were White, non-Hispanic, and middle class. Participants navigated under barriers normalized to their standing height (overhead, eye, chest, hip, and knee heights). Decreases in barrier height required lower postures for passage. Every participant altered their initial walking posture according to barrier height for every trial, and all but two 13-month-olds found solutions for passage. Compared to infants, adults displayed a wider variety of strategies (squat-walking, half-kneeling, etc.), found more appropriate solutions based on barrier height (ducked at eye height and low crawled at knee height), and implemented their solutions more quickly (within 4 s) and accurately (without bumping their heads against the barrier). Infants frequently crawled even when the barrier height did not warrant a low posture, displayed multiple postural shifts prior to passage and thus took longer to go, and often bumped their heads. Infants' improvements were related to age and walking experience. Thus, development of flexibility likely involves the contributions of multiple domains-motor, perception, and cognition-that facilitate strategy selection and implementation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The development of tool use: Planning for end-state comfort.

Some grips on the handle of a tool can be planned on the basis of information directly available in the scene. Other grips, however, must be planned on the basis of the final position of the hand. "End-state comfort" grips require an awkward or uncomfortable initial grip so as to later implement the action comfortably and efficiently. From a cognitive perspective, planning for end-state comfort requires a consistent representation of the entire action sequence, including the latter part, which is not based on information directly available in the scene. Many investigators have found that young children fail to demonstrate planning for end-state comfort and that adultlike performance does not appear until about 12 years of age. In 2 experiments, we used a hammering task that engaged children in a goal-directed action with multiple steps. We assessed end-state-comfort planning in novel ways by measuring children's hand choice, grip choice, and tool implementation over multiple trials. The hammering task also uniquely allowed us to assess the efficiency of implementation. We replicated the previous developmental trend in 4-, 8-, and 12-year-old children with our novel task. Most important, our data revealed that 4-year-olds are in a transitional stage during which several competing strategies were exhibited during a single session. Preschoolers changed their grip within trials and across trials, indicating awareness of errors and a willingness to sacrifice speed for more efficient implementation. The end-state-comfort grip initially competes as one grip type among many but gradually displaces all others. Children's sensitivity to costs and drive for efficiency may motivate this change. (PsycINFO Database Record

The context preexposure facilitation effect in mice: a dose-response analysis of pretraining scopolamine administration.

The context preexposure facilitation effect (CPFE) is an elaboration of contextual fear conditioning and refers to enhanced contextual conditioning resulting from preexposure to the context prior to a separate, brief context-shock episode. A version of the CPFE developed by Rudy and colleagues in rats has demonstrated greater sensitivity to pre-training hippocampal insult relative to standard contextual fear conditioning preparations. Our aim was to adapt the Rudy CPFE procedures to mice. In Experiment 1 we compared performance of young adult male C57BL6/J mice on two versions of the CPFE. One version - not previously used in mice - adapted methods established by Rudy and colleagues, and the other CPFE task replicated procedures previously established in this mouse strain by Gould and colleagues. In Experiment 2 we compared the effects of pre-training intraperitoneal administration of moderate levels of scopolamine or methylscopolamine on contextual conditioning between mice trained using the Rudy CPFE method and a separate group trained using standard contextual fear procedures. Scopolamine is a muscarinic cholinergic receptor antagonist that impairs hippocampal function. Robust freezing to the conditioning context was observed in mice trained using the Rudy CPFE method (Experiment 1), and greater scopolamine-induced impairments in contextual freezing were observed using this CPFE method relative to mice trained using standard contextual fear procedures (Experiment 2). These findings support use of the Rudy CPFE task as a behavioral assay for hippocampal function in mice.

Trace eyeblink conditioning is impaired in α7 but not in ß2 nicotinic acetylcholine receptor knockout mice.

Nicotinic acetylcholine receptors (nAChRs) are essentially involved in learning and memory. A neurobiologically and behaviorally well-characterized measure of learning and memory, eyeblink classical conditioning, is sensitive to disruptions in acetylcholine neurotransmission. The two most common forms of eyeblink classical conditioning - the delay and trace paradigms - differentially engage forebrain areas densely-populated with nAChRs. The present study used genetically modified mice to investigate the effects of selective nAChR subunit deletion on delay and trace eyeblink classical conditioning. α7 and ß2 nAChR subunit knockout (KO) mice and their wild-type littermates were trained for 10 daily sessions in a 500-ms delay or 500-ms trace eyeblink conditioning task, matched for the interstimulus interval between conditioned stimulus and unconditioned stimulus onset. Impairments in conditioned responding were found in α7 KO mice trained in trace - but not delay - eyeblink conditioning. Relative to littermate controls, ß2 KO mice were unimpaired in the trace task but displayed higher levels of conditioned responding in delay eyeblink conditioning. Elevated conditioned response levels in delay-conditioned ß2 KOs corresponded to elevated levels of alpha responding in this group. These findings suggest that α7 nAChRs play a role in normal acquisition of 500 ms trace eyeblink classical conditioning in mice. The prominent distribution of α7 nAChRs in the hippocampus and other forebrain regions may account for these genotype-specific acquisition effects in this hippocampus-dependent trace paradigm.