Robert Numan

The Behavioral Neuroscience of the Septal Region

From the contents: Preface On the Basic Architecture of the Septal Region (Larry W. Swanson/Pierre-Yves Risold) Neuronal Networks that Control the Septal Pacemaker System: Synaptic Interconnections between the Septal Complex Hippocampus, Supramammillary Area and Median Raphe (Csaba Leranth/ Robert P. Vertes) Cellular Pharmacology at Synapses Within the Septal Complex (Joel P. Gallagher/ Patricia Shinnick- Gallagher/William H. Griffith) Septal Orchestration of Hippocampal Networks Dynamics (James J. Chrobak) Septal Modulation of Hippocampal Dynamics: What is the Function of the Theta Rhythm? (Michael E. Hasselmo) The Medial Septum: Node of the Ascending Brainstem Hippocampal Synchronizing Pathways (Brian H. Bland) Trans-Synaptic Mechanisms Controlling Cholinergic Neuronal Activation in the Septo- Hippocampal and nBM-Cortical Pathways: Differential Roles in Memory and Attentional Processes? (Thomas P. Durkin/Pierre Cazala/Rene Garcia) The Septal Region and Social Behavior (Teige Sheehan/ Michael Numan) The Septum and Anxiety (Dallas Treit/Janet Menard) The Septal Complex as Seen Through the Context of Fear (Peter D. Sparks/Joseph E. LeDoux) And much more....

Cortical-limbic mechanisms and response control: A theoretical review

The literature dealing with the behavioral effects produced by lesions of the septum, frontal cortical areas, and the hippocampus is reviewed. It is concluded that the dorsomedial septum, the dorsolateral frontal cortex (and homologous structures), and the dorsal hippocampus form a nodal point within a larger neuronal system that is involved in response regulation. A model describing the response regulatory processes mediated by this frontal cortical-limbic system is proposed. Motor programs are written in frontal cortex and temporarily stored in hippocampus. Feedback stimuli derived from response initiation and maintenance are compared against the stored hippocampal motor program. If the feedback information matches with the expected outcomes dictated by the motor program, the response sequence is terminated. If comparator deviations arise, the frontal cortical areas are signaled of error and a new motor program is written. Hippocampal theta activity is postulated to be a correlate of comparator activation and feedback analysis.

Multiple exposures to ethanol facilitate intravenous self-administration of ethanol by rats

In Experiment 1, male hooded rats (N=11) were implanted with jugular cannulas, and housed in sound attenuated operant chambers 24hr/day. The rats were exposed to periodic cycles of forced ethanol infusions (30% v/v, 9-16 g/kg/day over 4-6 days for each cycle). Following each cycle, forced infusions were discontinued, but the rats were allowed access to lever for self-administration of ethanol on a fixed ration 1 schedule (FR1). Each lever press infused 0.2 ml of ethanol (20% v/v). The rats were maintained on self-administration for at least 24 hr. If a rat did not develop self-administration behavior (SAB) within 24 hr, the next forced cycle fo ethanol exposure was initiated. Eight of the 11 rats developed SAB after a mean of 5.25 cycles of exposure to ethanol, and were then tested for a mean of 15 days on self-administration under FR1, FR2, and FR3 schedules of reinforcement. All rats were tested on FR1 and days of self-administered a mean of 10.43 g ethanol/kg/day over a mean of 10.75 days. Four rats were subsequently tested on FR2 and FR3 and increased lever presses in order to maintain daily ethanol intake comparable to FR1. Following self-administration testing, the rats were placed on withdrawal and exhibited mild to severe withdrawal symptoms, suggesting that SAB maintained physical dependence. In Experiment 2, rats (N=6/group) were allowed to self-infuse either saline or ethanol (20% v/v). These rats had no prior exposure to either saline or ethanol, and forced infusion were never administered. The rats remained in their operant chambers for 21 days under FR1 contingencies. Each lever press led to a 0.2 ml infusion. None of the rats developed SAB, but the saline controls made more lever presses than the ethanol rats (p less than 0.01). These results suggest that the ethanol parameters yielding SAB in Experiment 1 are aversive to ethanol naive rats.

Effects of medial septal lesions on operant delayed alternation in rats

The septohippocampal system regulates spatial behavior, memory and response flexibility. This experiment determined which of these functions is disrupted by medial septal lesions which impair operant delayed alternation in rats. Male hooded rats received either medial septal lesions or a control operation. Following recovery, they were reinforced for alternating left and right lever presses in an operant chamber. The effects of various delays (0, 10 and 20 s), and exteroceptive cues were assessed. Medial septal lesions did not impair alternation performance at the 0-s delay, but did produce severe impairments at the 10- and 20-s delays. An exteroceptive light cue which reduced the spatial requirements of the task did not ameliorate this impairment. However, an exteroceptive light cue which reduced the working-memory requirements of the task did ameliorate the lesion-induced deficit on delayed alternation. While the lesioned rats also made more perseverative errors than the controls, statistically removing this influence from the data did not modify the results. These data suggest that medial septal lesions in rats impair operant delayed alternation by disrupting the general process of working-memory rather than spatial behavior or response flexibility.

Effect of morphine on rectal temperature after acute and chronic treatment in the rat.

Abstract 1. 1. In naive male rats morphine sulfate administered intraperitoneally in doses less than 25 mg/kg produced hyperthermia, while higher doses produced hypothermia. 2. 2. In morphine tolerant rats, morphine produced only hyperthermia at all doses with a markedly reduced time of onset. 3. 3. When morphine was acutely administered intravenously, all doses tested (2,5,10 and 20 mg/kg) led to an initial hypothermia; hyperthermia subsequently occurred at doses 2,5 and 10 mg/kg, but not at 20 mg/kg. 4. 4. Naltrexone (5 mg/kg) antagonized both the hyperthermic and hypothermic response to intraperitoneally administered morphine, and when the hypothermic response was antagonized, hyperthermia occurred. 5. 5. Adrenalectomy retarded the hyperthermic effects of intraperitoneally administered morphine in both naive and tolerant subjects. 6. 6. It is suggested that hypothermia is a primary action of morphine on central thermoreceptors, and that certain components of the hyperthermic response are induced indirectly, perhaps through hormones of the adrenal glands.

Effects of medial septal lesions on an operant delayed Go/No-Go discrimination in rats

Male hooded rats received either a medial septal lesion or a control operation. The rats were then tested on an operant go/no-go discrimination task, first without a delay contingency (20 days), followed by 25 days under an 8-s delay. A discrete trial procedure with symmetrical reinforcement was used. Each trial began with the operant chamber darkened, except for back illumination of a centrally located press panel. Depression of this panel extinguished the back light and initiated a random presentation of either the go stimulus (2800 Hz tone) or the no-go stimulus (10 Hz pulsing light) for 3 s. Stimulus termination initiated the appropriate delay contingency (0 s or 8 s), which was followed by the cued availability of a lever for 2 s. If the rat pressed the lever on go trials, or refrained from pressing the lever on no-go trials, a food pellet was delivered. The data (% correct responses) were averaged over 5-day blocks. Overall, the septal-lesioned rats performed significantly better than the control rats under both O-s delay (p < 0.025) and 8-s delay (p < 0.001) contingencies. Although there was not a significant difference between the groups during the last block of the O-s delay (septals 93% correct, controls 89% correct, p > 0.05) or the first block of the 8-s delay (septals 54% correct, controls 53% correct, p > 0.05), the septal-lesioned animals performed significantly better than the controls during all the remaining phases of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Medial septal lesions impair performance on a preoperatively acquired delayed alternation task

Male hooded rats were preoperatively trained to perform an operant delayed alternation (DA) task. The rats were tested, for 10 days each, on DA at 5-, 10-, 20-, and 30-s delays. The rats were then randomly assigned to serve as control subjects or receive a medial septal lesion. Following surgical recovery the rats were retested on DA in the exact manner as they were tested preoperatively. Prior to surgery the groups did not differ, but all rats improved over days of testing, and performed better at short delays than at long delays. In contrast, group differences were obvious following surgery, with the septal-lesioned subjects showing a clear impairment. The control subjects ranged between 85% correct (end of 5-s delay) to 65% correct (end of 30-s delay), while the septal-lesioned rats ranged between 72% correct (end of 5-s delay) to 50% correct (end of 30-s delay). The results are discussed in terms of a working memory impairment produced by the septal lesions.

Septal Modulation of the Working Memory for Voluntary Behavior

A large body of data now supports the view that portions of the septohip-pocampal system play a critical role in the modulation of specific memory processes in both people and animals (Squire 1992; von Cramon and Schuri 1992; Cohen and Eichenbaum 1993). In people, there is good evidence that the hippocampal system modulates declarative memory (Squire 1992; Cohen and Eichenbaum 1993), and other neural systems mediate nonde-clarative memory (Schacter, Chiu, and Ochsner 1993; Squire, Knowlton, and Musen 1993; Zola-Morgan and Squire 1993). In people, declarative memory can be defined as “the capacity for conscious recollections about facts and events,” and nondeclarative memory as “a heterogenous collection of non-conscious abilities that includes the learning of skills and habits” (Zola- Morgan and Squire 1993, p. 547). In addition, Mishkin et al. (1997) have argued that, in people, the semantic (facts) and episodic (events) components of declarative memory might be modulated by different portions of the hippocampal system, with the hippocampus proper playing a stronger role in the regulation of episodic memory, whereas the perirhinal and parahippocampal cortex more strongly mediate semantic memory. In that study, three patients who suffered relatively selective damage to the hippocampus proper early in life subsequently acquired a reasonable base of semantic knowledge, but evidenced severe impairments in episodic memory.

Induction of physical dependence upon ethanol in rats using intravenous infusion

Intravenous infusions were used to produce physical dependence upon ethanol in rats. The procedure proved to be safe, rapid, and reliable. Ethanol (30% v/v) was administered over a 7-day period. The mean daily dose ranged from 10--14 g/kg/day. Control rats were exposed to a comparable procedure except that saline, rather than ethanol, was infused. All ethanol treated rats that survived the intoxication period (n = 11) showed signs of physical dependence (moderate to severe, n = 8; mild, n = 3) following ethanol withdrawal. Saline treated rats (n = 8) did not show any of these symptoms. The most reliable ethanol withdrawal signs observed were: spontaneous seizure (n = 7), audiogenic seizure (n = 7), tremors (n = 6), tail stiffening (n = 10) and body rigidity (n = 9). These symptoms were analyzed in terms of their hour of onset and hour of maximum intensity following ethanol withdrawal. Application of the intravenous method for the study of ethanol self-administration is discussed.

A Prefrontal-Hippocampal Comparator for Goal-Directed Behavior: The Intentional Self and Episodic Memory.

The hypothesis of this article is that the interactions between the prefrontal cortex and the hippocampus play a critical role in the modulation of goal-directed self-action and the strengthening of episodic memories. We describe various theories that model a comparator function for the hippocampus, and then elaborate the empirical evidence that supports these theories. One theory which describes a prefrontal-hippocampal comparator for voluntary action is emphasized. Action plans are essential for successful goal-directed behavior, and are elaborated by the prefrontal cortex. When an action plan is initiated, the prefrontal cortex transmits an efference copy (or corollary discharge) to the hippocampus where it is stored as a working memory for the action plan (which includes the expected outcomes of the action plan). The hippocampus then serves as a response intention-response outcome working memory comparator. Hippocampal comparator function is enabled by the hippocampal theta rhythm allowing the hippocampus to compare expected action outcomes to actual action outcomes. If the expected and actual outcomes match, the hippocampus transmits a signal to prefrontal cortex which strengthens or consolidates the action plan. If a mismatch occurs, the hippocampus transmits an error signal to the prefrontal cortex which facilitates a reformulation of the action plan, fostering behavioral flexibility and memory updating. The corollary discharge provides the self-referential component to the episodic memory, affording the personal and subjective experience of what behavior was carried out, when it was carried out, and in what context (where) it occurred. Such a perspective can be applied to episodic memory in humans, and episodic-like memory in non-human animal species.