Ann E. Fitchett

Medial septal cholinergic neurons are necessary for context-place memory but not episodic-like memory.

Loss of cholinergic cortical input is associated with diseases in which episodic memory impairment is a prominent feature, but the degree to which this neurochemical lesion can account for memory impairment in humans with neurodegenerative diseases remains unclear. Removal of cholinergic input to hippocampus impairs some of its functions in memory, perhaps by reducing the plasticity of information representation within the hippocampus, but the role of cholinergic hippocampal input in episodic‐like memories has not been investigated. To address this question, we tested rats with selective lesions of basal forebrain neurons in the medial septum and vertical limb of the diagonal band (MS/VDB), which contains hippocampal‐projecting cholinergic neurons, on a task of integrated memory for objects, places, and contexts (“what–where–which” memory). This task serves as a rodent model of human episodic memory (episodic‐like memory) and is sensitive to damage to the hippocampal system. Rats with lesions of cholinergic MS/VDB neurons performed as well on the what–where–which task as controls, but were impaired in a task that simply required them to associate places with contexts (“where–which” memory). Thus, episodic‐like memories that rely on the hippocampus do not require cholinergic neuromodulation to be formed. Nevertheless, some more specific aspects of where–which memory, which may be more dependent on the plasticity of hippocampal spatial representations, require acetylcholine. These results suggest that cholinergic projections to hippocampus are not necessary for episodic memory and, furthermore, that hippocampal spatial representations may be to some extent dissociable from episodic memory function.

There's no place like home: Cage odours and place preference in subordinate CD-1 male mice

Prior studies using mice have shown that scent marks are an important source of information and can cause behavioural changes in other individuals. Studies have also shown that scent marks in the environment can affect the outcome of social interactions between mice. We used conditioned place preference tests to investigate whether CD-1 male mice (Mus musculus) are reinforced by olfactory cues from the home cage. Soiled bedding from the home cage was presented in the initially less preferred chamber of the apparatus to determine whether this association would reduce the unconditioned preference for one chamber over the other. We tested the effects of social rank and housing condition by comparing the performance of dyads that were polarised into dominant and subordinate relationships, both when paired and when separated, with mice that were isolated throughout. The development of conditioned place preference (CPP) supported by home cage odours was influenced by social rank but not by housing condition. Only subordinate mice showed CPP to home cage odours, and this effect was seen irrespective of whether they were housed with a dominant cage mate or alone. Neither dominant (paired or separated) nor isolated mice showed any change in their preference for the chamber associated with home cage odours. This suggests that the smell of home is a more powerful reinforcer for subordinate mice in that it can produce contextual conditioning to the environment in which it is experienced.

Urinary corticosterone measures: Effects of strain and social rank in BKW and CD-1 mice

We used urinary assays as a non-invasive method to examine corticosterone levels in two outbred strains of male laboratory mice (BKW and CD-1). Measures were taken before and after 2 weeks of pair housing, to examine the effects of social stress. We found that CD-1 mice had significantly higher corticosterone levels compared to BKW mice both before and after pairing. Behavioural measures provided evidence that, when paired, both strains of mice polarised into dominants and subordinates, with a higher overall incidence of aggressive acts in the BKW mice. Some pairings had to be separated to prevent injuries so the pairing procedure introduced a selection for non-aggressive socially tolerant mice. Social status was nevertheless found to be associated with pre-existing differences in urinary corticosterone in the CD-1 strain: mice that later became dominant had overall lower levels of urinary corticosterone compared to subordinates. In conclusion, urinary corticosterone levels indicated clear differences in physiology, likely to be related to the adrenal stress response, dependent on both strain and social status. Thus, this non-invasive measure could help to predict the welfare outcomes of social housing and how these may depend on dominance status, rather than overall levels of aggression, in different strains of mice.

Low-level repeated exposure to diazinon and chlorpyrifos decrease anxiety-like behaviour in adult male rats as assessed by marble burying behaviour

Occupational exposure to organophosphate (OPs) pesticides is reported to increase in the risk of developing anxiety and depression. Preclinical studies using OP levels, which inhibit acetylcholinesterase activity, support the clinical observations, but little is known of the effects of exposure below this threshold. We examined the effects of low level OP exposure on behaviours and neurochemistry associated with affective disorders. Adult rats were administered either diazinon (1 mg/kg i.p.) which is present in sheep dip and flea collars, chlorpyrifos (1 mg/kg i.p.) which is present in crop sprays, or vehicle for 5 days. OP exposure did not affect acetylcholinesterase activity (blood, cerebellum, caudate putamen, hippocampus, prefrontal cortex), anhedonia-like behaviour (sucrose preference), working memory (novel object recognition), locomotor activity or anxiety-like behaviour in the open field arena. In contrast OP exposure attenuated marble burying behaviour, an ethological measure of anxiety. The diazinon-induced reduction in marble burying persisted after exposure cessation. In comparison to vehicle, dopamine levels were lowered by chlorpyrifos, but not diazinon. 5-HT levels and turnover were unaffected by OP exposure. However, 5-HT transporter expression was reduced by diazinon suggesting subtle changes in 5-HT transmission. These data indicate exposure to occupational and domestic OPs, below the threshold to inhibit acetylcholinesterase, can subtly alter behaviour and neurochemistry.

Gene expression analysis reveals chronic low level exposure to the pesticide diazinon affects Psychological Disorders gene sets in the adult rat

Chronic low level exposure to organophosphate (OPs) pesticides in adulthood has been linked to adverse neurobehavioural deficits and psychological disorder symptoms, although this remains a contentious issue. The OP-induced biological changes that could underlie these effects are unclear. We assessed gene expression changes following chronic low level exposure to diazinon, a pesticide with a high dietary exposure risk. Adult male rats were orally exposed to diazinon (0, 1, 2mg/kg, 5days a week for 12 weeks). After 4 weeks, marble burying behaviour was lower in diazinon exposed rats than vehicle exposed rats; this difference persisted for 8 weeks. Chronic diazinon exposure did not significantly inhibit acetylcholinesterase activity, the primary mechanism of action of high level OPs. Affymetrix GeneChip® HT RG-230 PM Arrays were used for gene profiling followed by Ingenuity Pathway analysis. In the hippocampus, the most significant gene expression changes caused by OP exposure were associated with Psychological Disorders, and Cell-To-Cell Signalling and Interaction functions. Genes encoding the AMPA3 glutamate receptor, glutaminase, dopamine transporter and tyrosine hydroxylase were up-regulated, whereas the gene encoding the GABAB1 receptor was down-regulated. In the dorsal raphe nucleus, genes associated with development and the Psychological Disorders function were significantly affected, including the up-regulation of the gene encoding the α1b-adrenoceptor, the major driver of serotoninergic (5-HT) neuronal activity. These data indicate that chronic exposure to diazinon in adulthood, below the threshold to inhibit acetylcholinesterase, stimulates glutamatergic, dopaminergic and serotonergic synaptic transmission which may underlie adverse neurological outcomes.

Spontaneous honeybee behaviour is altered by persistent organic pollutants

The effect of environmental pollutants on honeybee behaviour has focused mainly on currently used pesticides. However, honeybees are also exposed to persistent organic pollutants (POPs). The aim of this laboratory based study was to determine if exposure to sublethal field-relevant concentrations of POPs altered the spontaneous behaviour of foraging-age worker honeybees. Honeybees (Apis mellifera) were orally exposed to either a sublethal concentration of the polychlorinated biphenyl (PCB) mixture Aroclor 1254 (100 ng/ml), the organochlorine insecticide lindane (2.91 ng/ml) or vehicle (0.01% DMSO, 0.00015% ethanol in 1M sucrose) for 1–4 days. The frequency of single event behaviours and the time engaged in one of four behavioural states (walking, flying, upside down and stationary) were monitored for 15 min after 1, 2, 3 and 4 days exposure. Exposure to Aroclor 1254 but not lindane increased the frequency and time engaged in honeybee motor activity behaviours in comparison to vehicle. The Aroclor 1254—induced hyperactivity was evident after 1 day of exposure and persisted with repeated daily exposure. In contrast, 1 day of exposure to lindane elicited abdominal spasms and increased the frequency of grooming behaviours in comparison to vehicle exposure. After 4 days of exposure, abdominal spasms and increased grooming behaviours were also evident in honeybees exposed to Aroclor 1254. These data demonstrate that POPs can induce distinct behavioural patterns, indicating different toxicokinetic and toxicodynamic properties. The changes in spontaneous behaviour, particularly the PCB-induced chronic hyperactivity and the associated energy demands, may have implications for colony health.