Memory Tests for evaluation of nootropic compounds

Y-Maze Discrimination

The Y-maze discrimination method can be used for investigation of electric footshock-motivated discrimination learning and memory in rats, mice, and other rodents. We have developed a computer-controlled automatic Y-maze suitable for studies of spatial alternation, brightness discrimination, and other procedures. In these experiments, animals learn the discrimination task in a short training session (e.g., 30 trials; 30 min duration). Memory retention can be tested in relearning or extinction sessions at different intervals after learning (e.g. , 24 hours later). In the spatial alternation paradigm, for example, the animal learns to alternate between two alleys of the maze (without intra-maze cues). In the brightness discrimination paradigm, the animal learns to discriminate between different illumination of the Y-maze alleys (e.g., light-dark discrimination). In each case, false runs (errors) are punished by electric footshocks. After the experiment, a number of different parameters give information on learning, memory, motor activity, footshock sensitivity, and other behavioral functions (number of errors, percent savings, latencies, inter-trial crossing, fecal boli, etc.).

(For further information see end of this page)
   

Recent publications:

Riedel, G., Wetzel, W., Reymann, KG. Computer-assisted shock-reinforced Y-maze training: a method for studying spatial alternation behaviour. Neuroreport 5, 2061-2064 (1994).

Riedel, G., Wetzel, W., Reymann, K. Metabotropic glutamate receptors in spatial and nonspatial learning in rats studied by means of agonist and antagonist application. Learning & Memory 2, 243-265 (1995)

Balschun, D. and Wetzel, W. Inhibition of group I metabotropic glutamate receptors blocks spatial learning in rats. Neurosci. Lett. 249, 41-44 (1998).

   
Radial Maze Learning

We use the 8-arm radial maze for investigations of spatial working and reference memory in rats and mice. The animals have to learn the localization of food pellets in certain arm(s) of the maze in daily training sessions (e.g., two trials per day; 5 or more training days). On the first day, the food-deprived animals received two habituation trials, i.e. all eight arms are baited with a food pellet. On the following days, only three arms are baited and the animals have to find the position of these arms. Entry into an unbaited arm is scored as reference memory error, and arm reentries are scored as working memory errors. Also, running time, time spent in alleys, sequences of arm visits, and other parameters are recorded. Instead of food reward, it is possible to use footshock reinforcement in these experiments. Furthermore, one can use special visual or tactile patterns in different arms of the maze for testing of non-spatial forms of discrimination.

(For further information see end of this page)
   

Recent publications:

Balschun, D., Manahan-Vaughan, D., Wagner, T., Behnisch, T., Reymann, K.G., Wetzel, W. A specific role for group I mGluRs in hippocampal LTP and hippocampus-dependent spatial learning. Learning & Memory 6, 138-152 (1999).

Schwegler H, Crusio WE.Correlations between radial-maze learning and structural variations of septum and hippocampus in rodents.Behav Brain Res. 67, 29-41 (1995).

Ammassari-Teule, M., Hoffmann, H.J., Rossi-Arnaud, C. Learning in inbred mice: strain-specific abilioties across three radial maze problems. Behav. Genet. 23, 405-412 (1993).

   
Shuttle-Box Discrimination

As a discrimination model gerbils (Meriones unguiculatus) are trained to discriminate tones (for example the direction in frequency-modulation) in a go/no-go paradigm. In combination with brain lesions (auditory cortex) the relevance of this brain areas in dicrimination learning can be evaluated.

A finegrain analysis of behavior recorded by a modified NOLDUS observer system is aimed at the differentiation of components of information processing. The influence of various acquired non-avoidance strategies as pre-experience were studied during the learning of a avoidance task. Behavioral events such as the attention response and the orienting response were quantified. Thereby, components of shuttle-box learning such as signal detection and signal evaluation were found. The influence of drugs which are in involved in learning and memory processes can be investigaed more in detail.

(For further information see end of this page)

Recent publications:

Wetzel, W., Wagner, T., Ohl, F.W., Scheich, H. Categorical discrimination of direction in frequency-modulated tones by Mongolian gerbils. Behav. Brain Res. 91, 29-39 (1998).

Wetzel, W., Ohl, F.W., Wagner, T., Scheich, H. Right auditory cortex lesion in Mongolian gerbils impairs discrimination of rising and falling frequency-modulated tones. Neurosci. Lett. 252, 115-118 (1998).

Ohl, F.W., Wetzel, W., Wagner, T., Rech, A., Scheich, H. Bilateral ablation of auditory cortex in Mongolian gerbil affects discrimination of frequency modulated tones but not of pure tones. Learning & Memory 6, 347-362 (1999).

Wetzel, W., Wagner, T., Ohl, F., and Scheich, H.: Categorical discrimination of direction in frequency-modulated tones by Mongolian gerbils. Behav. Brain Res. 91, 29-39 (1998).

Wetzel, W., Ohl, F.W., Wagner, T., and Scheich, H.: Right auditory cortex lesion in Mongolian gerbils impairs discrimination of rising and falling frequency-modulated tones. Neurosci. Lett. 252, 115-118 (1998).

Ohl, F.W., Wetzel, W., Wagner, T., Rech, A., and Scheich, H.: Bilateral ablation of auditory cortex in Mongolian gerbil affects discrimination of frequency modulated tones but not of pure tones. Learning & Memory 6, 347-362 (1999).

Bischof, A., Stark, H., Wagner, T., and Scheich, H.: The inhibitory influence of an acquired escape strategy on subsequent avoidance learning in gerbils. Neurosci. Lett. 281, 175-178, (2000).

Stark, H., Bischof, A., Wagner, T., and Scheich, H.: Increase of extracellular dopamine in prefrontal cortex of gerbils during acquisition of the avoidance strategy in the shuttle-box.
Neurosci. Lett. 284, 77-80 (1999).

Stark, H., Bischof, A., Wagner, T., and Scheich, H.: Stages of avoidance stragegy formation in gerbils are correlated with dopaminergic transmission activity. Eur. J. Pharmacol, 405, 263-275 (2000).
   

Effect of unilateral auditory cortex lesion in Mongolian gerbils on discrimination of ascending and descending frequency- modulated tones tested in a shuttle-box go/no go paradigm.

Fluorodeoxyglucose (FDG) autoradiograph of horizontal brain section of a right auditory cortex lesioned animal (AC: auditory cortex; arrow: lesion).

Group mean values of response differences (correct minus false responses) during 8 days of discrimination learning (ConL: sham-lesion left; ConR: sham-lesion right; LesL: lesion left; LesR: lesion right; 1,2: P<0.05; 3: P<0.02; 4: P<0.01).

Performance profiles during the stages of signal detection (-), and signal evaluation (-) of avoidance learning in a shuttle-box, and retrieval (-) of avoidance response (A). Temporal profiles of relative DA content in brain dialysates during the signal detection (-), signal evaluation (-), and retrieval of the avoidance response (-) (B).
  

Fear Conditioning

Conditioning of fear (Pavlovian fear conditioning), a learning paradigm with high emotional components, can be investigated by a simple training procedure. Usually, the animal (rats, mice, other species) is observed in a new environment (a small cage with a grid floor for application of footshocks) for a short period of time. After 2 minutes, one gives a tone stimulus of 30 sec duration and then an electric footshock of 2 sec duration. The training session is finished after a total time of 3 minutes. After a certain interval, e.g. 24 hours, retention of fear conditioning is tested using two different procedures. (a) For testing of context-dependent fear conditioning (hippocampus-dependent), the animal is observed in the same cage as in the training session, without the tone stimulus. (b) For testing of cue-dependent fear conditioning (hippocampus-independent) one observes the animal in a new cage and give the tone stimulus (the same stimulus as used in the training session). The quantitative amount of fear conditioning is estimated by the percentage of freezing behavior (immobility except breathing) related to the total observation time.

(For further information see end of this page)

Recent publications:

Henrich-Noack, P., Wetzel, W. and Reymann, K.G. Freezing behaviour in gerbils with hippocampal CA1 damage after ischaemia. Eur. J. Neurosci. 12, Suppl.11, 117 (2000).

Stiedl O, Palve M, Radulovic J, Birkenfeld K, Spiess J.
Differential impairment of auditory and contextual fear conditioning by protein synthesis inhibition in C57BL/6N mice.Behav Neurosci. 113, 496-506 (1999).

Maren S.Overtraining does not mitigate contextual fear conditioning deficits produced by neurotoxic lesions of the basolateral amygdala.J Neurosci. 18, 3088-97 (1998).
   

For further information please contact: