Spatial deficits

Neurofilament and peripherin mutations were reported in rare forms of ALS (Gros-Louis et al., 2004 Leung et at., 2004), leading researchers to develop animal models bearing these mutations (Millecamps et al., 2006). Although these mice developed no evident MND, some exhibited moderate sensorimotor and spatial deficits probably due to the observed reduction in conduction velocity. 

Schantz, S.L., J. Moshtaghian, and D.K. Ness. 1995. Spatial learning deficits in adult rats exposed to ortho-substituted PCB congeners during lactation and gestation. Fundam. Appl. Toxicol. 26 117-126. 

The exact nature of the deficit produced by NMDA antagonists and the interpretation of results has been questioned. It is difficult to ignore the possibility that sensorimotor impairment, however subtle, may mediate the apparent spatial learning deficit in rats (Keith and Rudy, 1990). The fact that animals exhibiting minimal LTP still demonstrate significant learning is also challenging (Bannerman et al., 1995). 

Ahmed FP, McLaughlin DP, Stanford SC, Stamford JA (2002) Maudsley reactive and non-reactive (MNRA) rats display hehavioral contrasts on exposure to an open field, the elevated plus maze or the dark-light shuttle hox. Abstract, FENS, Paris, France Ammassari-Teule A, Milhaud JM, Passino E, Restivo L, LassaUe JM (1999) Defective processing of contextual information may he involved in the poor performance of DBA/2 mice in spatial tasks. Behav Genet 29 283-289 Anisman H, Zalcman S, Shanks N, Zacharko RM (1991) Multisystem regulation of performance deficits induced hy stressors an animal model of depression. In Boulton AA, Baker GB, Martin-lverson MT (eds) Animal models in psychiatry, vol 2. Humana Press, Clifton, pp 1-59... 

Oitzl MS, De Kloet ER (1992) Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. Behav Neimosci 106 62-71 Oitzl MS, de Kloet ER, Joels M, Schmid W, Cole TJ (1997) Spatial learning deficits in mice with a targeted glucocorticoid receptor gene disruption. Eur J Neurosci 9 2284-2296... 

It is striking that the behavioural consequences of an impairment of as GABAa receptors are opposite to those of a NMDA receptor deficit. While mice with a deficit in hippocampal NMDA receptors (NRI-CAl knockout) show a deficit in the formation of spatial and temporal memory (Tsien et al. 1996 Tang et al. 1999), the mice with a deficit in as GABAa receptors display an improvement in hippocampal spatial and temporal memory performance. Thus, it appears that these two receptor systems play a complementary role in controlling neuronal processing in the hippocampus. 

A deficit in as GABAa receptor activation is associated with an improved hippocampal performance in temporal and spatial memory tasks (see above)... 

Quartermain et al. 1993, 1994 Rowan et al. 1990 Winter and Petti 1987). Also, low doses of gepirone and atropine, which individually fail to modify rat performance in a spatial task, when administered together impair performance [Barrett and Rowan 1990]. Similarly, the selection of a single dose of MDL 73,005EF that did not impair the acquisition or recall of a task in the Morris water maze enhanced the deficits caused by gepirone or atropine [Barrett and Rowan 1992]. 

To reveal the cognition-enhancing potential of the S-HTj antagonists, studies in age-related memory impairment have been carried out with psy-chiatrically healthy subjects impaired with scopolamine and patients with dementia. In a randomized double-blind, double-dummy, four-way crossover study in a small number of subjects, each psychiatrically healthy male subject received placebo, scopolamine [0.4 mg im], scopolamine plus alosetron [10 J,g iv], or alosetron [250 Jg] [Preston 1994 Preston et al. 1991). Assessments of verbal and spatial memory, sedation, and sustained attention were performed before and after treatment. The main results from the study were that scopolamine induced robust deficits on all primary variables measured, the reduction in verbal and spatial memories being attenuated by 10- Jg and 250- Jg doses of alosetron, respectively. No effects on the sedation or on changes in attention were noted. 

Studies of animals with central cholinergic lesions produced by either pharmacological inhibition of choline uptake or direct excitotoxic lesions of basal forebrain cholinergic neurons have shown highly specific attentional deficits (Muir et al. 1992 Robbins et al. 1989). These animals showed deficits that might be predicted from studies of humans with AD that is, they showed increased response latency and increased responsiveness to irrelevant sensory stimuli. Studies by Vidal (1994b) have shown that administration of a nicotinic antagonist into rat prefrontal cortex impairs performance on spatial... 

Buchsbaum MS, Wu J, DeLisi EE, et al Frontal cortex and basal ganglia metabolic rates assessed by positron emission tomography with [18F]2-deoxyglucose in affective illness. J Affect Disord 10 137-152, 1986 Buhot MC, Patra SK, Naili S Spatial memory deficits following stimulation of hippocampal 5-HTjj receptors in the rat. Eur J Pharmacol 285 221-228, 1995... 

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