Electrode tip alignment and self-stimulation: Influence of anodal hyperpolarization

Phystology and Behavior, Vol 11, pp. 581-583. Brain Research Pubhcatlons Inc , 1973 Printed m the U S.A.

BRIEF COMMUNICATION Electrode Tip Alignment and Self-Stimulation: Influence of Anodal Hyperpolarization 1 IMRE SZABO

Neurophys~ologwal Research Group of the Hungarian Academy of Sciences bTstitute of Phystology, Umverslty Medical School, Pecs, Huugao' AND

PETER M MILNER

Department of Psychology, McGtll UlllverslO', Montreal, Canada

( R e c e i v e d 21 F e b r u a r y 1 9 7 3 )

SZABO, I AND P. M. MILNER. Electrode ttp ahgnment and self-stunulatton influence o/ anodal hyperpolartzatton PHYSIOL BEHAV. 11(4) 5 8 1 - 5 8 3 , 1973 -Smusoldal current stmmlates the reinforcement system more effectively when the poles of bipolar electrodes m the posterior hypothalamus and ventral tegmentum are oriented m the medm-lateral direction than when they are aligned antero-postenorly The influence of pole onentanon on self-stlmulatmn is, however, remarkably less when the mtracranml electrical snmuh consist of trams of short rectangular pulses Saglttal spread of rewarding excltatmn seems to be impaired when 60 Hz smusmdal current is apphed through antero-postenor electrodes because the 8 3 msec-long periods of hyperpolanzatmn at one pole block transnussmn of impulses generated at the same time by the hypopolarxzmg current at the other pole When 0 2 msec current pulses are used, the hyperpolanzatmn block is too brief to prevent conductmn of the lrnpluses generated at the other pole The result supports the theory that axons of the reinforcement path in the hypothalamus conduct m the antero-postenor dlrect~on Self-stimulation Lateral hypothalamus Electrode tip orlentatmn

Ventral tegmental area

R E C E N T o b s e r v a t i o n s i n d i c a t e t h a t actlvataon o f reverberatory loops made up of the path neurons of the medial f o r e b r a m b u n d l e as responsable for lateral h y p o t h a l a m a c s e l f - s t i m u l a t i o n [ 2 ] . Since t h e a x o n s o f t h e p a t h n e u r o n s b i f u r c a t e near t h e s o m a t a to p r o j e c t rostrally a n d caudally [ 1 ], t h e r e v e r b e r a t o r y o r c u l t s of the n e u r o n s y s t e m are n o t r a n d o m l y o r i e n t e d wath respect to the axes of t h e b r a i n T h e a x o n s m t h e r e v e r b e r a t o r y loops c o n d u c t e x c a t a t m n m o s t l y in sagittal d l r e c t m n s , s u c h as a n t e r o - p o s t e r l o r l y a n d p o s t e r o - a n t e n o r l y As a c o n s e q u e n c e , a bapolar e l e c t r o d e w h o s e taps are a h g n e d a n t e r o - p o s t e n o r l y , s h o u l d be pessamal m s u p p o r t i n g lateral h y p o t h a l a m l c self-stamulat~on, since t h e sagattal p r o p a g a t m n of the r e w a r d i n g excatatlon g e n e r a t e d at o n e e l e c t r o d e pole ( c a t h o d e ) as b l o c k e d at t h e o t h e r pole ( a n o d e ) , as mdxcated m t h e u p p e r diagram of Fig 1 Thin e x p e c t a t i o n as s u p p o r t e d b y findings o f Szabo

Path neuron system of MFB

a n d Mllner [3] o b t a i n e d b y d e t e r m i n i n g s e l f - s t i m u l a t i o n t h r e s h o l d s for 60 Hz s m u s o l d c u r r e n t a p p h e d t h r o u g h m e d l o - l a t e r a l l y and a n t e r o - p o s t e n o r l y alagned b i p o l a r electrodes. However, it could n o t be d e t e r m i n e d f r o m thas s t u d y w h e t h e r t h e hagher self-st~mulatmn t h r e s h o l d s gwen by a n t e r o - p o s t e r i o r e l e c t r o d e s were i n d e e d due to a n o d a l h y p e r p o l a n z a t a o n or w h e t h e r t h e y a p p e a r e d as a conseq u e n c e of t h e fact t h a t e i t h e r t h e t h r e s h o l d to e h m t direct dascharges in t h e r e s p o n s i b l e e l e m e n t s or the n u m b e r of excited r e w a r d i n g e l e m e n t s changed as t h e spataal oraentat l o n of t h e b i p o l a r e l e c t r o d e s was v a n e d . In o r d e r t o arrive at a sangle a n t e r p r e t a t l o n for this finding, t h e i n f l u e n c e of a n o d a l h y p e r p o l a n z a t l o n was e x p l o r e d an the self-stamulatlon e x p e r a m e n t s r e p o r t e d here The effectaveness o f smusoxdal c u r r e n t and s h o r t r e c t a n g u l a r pulses was c o m p a r e d using b i p o l a r e l e c t r o d e s w h o s e poles

1Supported by National Research Council of Canada, Grant APA 66 to Peter M Mflner 581

582

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PULSE CURRENT(pA) } IG 1 The upper diagram shows how impulses pass ummpeded in the A-P direction when bipolar electrode tips are oriented in the M-L plane, but when they are aligned in the A-P plane the impulses may be blocked by anodal polarization in the ascending path during the half cycle of a sine wave when the anterior electrode tip is positive, and in the descending path by the posterior electrode tip during the other half cycle. The two graphs show the rate of self-stimulation as a function of stmmlatlng current applied through medJo-laterally (M-C) and antero-posterlorly (A-P) aligned bipolar electrodes As there were even numbers of rats in all tile groups, median curves were plotted by averaging the two individual curves In the middle of each dlStrlbuo lion The ends of the vertical bars indicate the points for these pmrs ol individual curves

TIP A L I G N M E N T A N D S E L F - S T I M U L A T I O N

583

were aligned e i t h e r in t h e medxo-lateral or t h e a n t e r o p o s t e r i o r plane. T h e i n f l u e n c e of a n o d a l h y p e r p o l a r i z a t l o n was e x p e c t e d to b e very m a r k e d w h e n 60 Hz slnusoldal c u r r e n t was applied because h y p e r p o l a n z x n g a n d d e p o l a r izing p e n o d s , lasting for a b o u t 8.3 msec a l t e r n a t e at each pole o f t h e e l e c t r o d e . In c o n t r a s t , r e w a r d i n g s t i m u l u s t r a i n s consisting of 0.2 msec r e c t a n g u l a r pulses s h o u l d d e m o n s t r a t e little effect o f a n o d a l h y p e r p o l a r l z a t l o n , since t h e h y p e r p o l a r i z a t i o n p e r i o d w o u l d be t o o b r i e f in r e l a t i o n t o the possible c o n d u c t i o n t i m e of r e w a r d i n g e x c i t a t i o n . METHOD T h i r t y - e i g h t male a l b i n o rats had b i p o l a r e l e c t r o d e s c h r o n i c a l l y i m p l a n t e d e i t h e r in t h e v e n t r a l t e g m e n t a l area or in t h e m e d i a l f o r e b r a i n b u n d l e at t h e level of the mammi1lary n u c l e a r c o m p l e x , as histological v e r i f i c a t i o n of t h e elect r o d e p l a c e m e n t s s h o w e d . T h e e l e c t r o d e s consisted o f t w o 0 25 m m n i c h r o m e wires, i n s u l a t e d e x c e p t at t h e i r cut tips TIp s e p a r a t i o n was a b o u t 0 . 1 - 0 . 2 m m T w e n t y - s i x b i p o l a r e l e c t r o d e s y i e l d i n g s e l f - s t i m u l a t i o n were o r i e n t e d so t h a t t h e i r poles were aligned in t h e medIo-lateral d i r e c t i o n . Tips o f 36 e l e c t r o d e s were o r i e n t e d a n t e r o - p o s t e r l o r l y . The a n i m a l s were t e s t e d in a S k i n n e r b o x p r o v i d e d w i t h a single pedal. Each b a r press delivered e i t h e r 60 Hz sinusoidal c u r r e n t for 0 . 1 7 5 sec or a 0.2 sec t r a i n of r e c t a n g u l a r pulses at 2 0 0 per sec. Pulse d u r a t i o n was 0 2 msec Stimulat i o n c u r r e n t was d e t e r m i n e d b y m e a s u r i n g t h e voltage across a 10 kg2 resistor in series w i t h t h e e l e c t r o d e . In t h e course of t h r e s h o l d d e t e r m i n a t i o n s , as described previously [3, 4, 5 ] , t h e c u r r e n t was available for 5-mln s t i m u l a t i o n test periods s e p a r a t e d b y 2-min off periods C u r r e n t level d u r i n g t h e first 5-min p e r i o d was capable of m a i n t a i n i n g a h i g h s e l f - s t i m u l a t i o n rate. F o r t h e n e x t 5-mln period, h o w e v e r , t h e c u r r e n t was r e d u c e d b y o n e step, and xt was r e d u c e d b y f u r t h e r steps at t h e b e g i n n i n g of each subse-

q u e n t 5-mln test p e r i o d u n t i l t h e a n i m a l s t o p p e d r e s p o n d lng. T h e c u r r e n t was t h e n r e t u r n e d to t h e initial level and t h e d e s c e n d i n g t h r e s h o l d d e t e r m i n e d 4 m o r e t i m e s in t h e same m a n n e r RESULTS AND DISCUSSION P l o t t i n g the m e a n n u m b e r of s e l f - s t i m u l a t i o n s determ i n e d at each c u r r e n t level at each e l e c t r o d e s e p a r a t e l y , it was easy to r a n k t h e e x a m i n e d loci o n t h e basis o f selfs t i m u l a t i o n t h r e s h o l d a n d also to select t h e m e d i a n rate vs c u r r e n t curve for each e l e c t r o d e g r o u p These curves s h o w n in Fig. 1 suggest t h a t t h e m e d i a n s e l f - s t i m u l a t i o n t h r e s h o l d was a b o u t 3 t i m e s higher in the a n t e r o - p o s t e r i o r t h a n in t h e m e d l o - l a t e r a l e l e c t r o d e g r o u p w h e n t h e c u r r e n t was smusoldal. T h e M a n n - W h i t n e y U test i n d i c a t e d a significant d i f f e r e n c e b e t w e e n t h e average s e l f - s t i m u l a t i o n t h r e s h o l d s o f a n t e r o - p o s t e r i o r and medlo-lateral g r o u p ( p < 0 01, onetailed t e s t ) If r e w a r d i n g s t i m u l a t i o n consisted o f 0.2 msec pulses, h o w e v e r , t h e i n f l u e n c e of e l e c t r o d e o r i e n t a t i o n , was greatly r e d u c e d , a l t h o u g h it still a p p r o a c h e d statistical significance ( M a n n - W h i t n e y test, 0.05 < p < 0 10). The o b s e r v e d d i f f e r e n c e in t h e effect of sinusoadal curr e n t a n d r e c t a n g u l a r pulse s t i m u l a t i o n i n d i c a t e t h a t a n o d a l h y p e r p o l a r i z a t l o n is t h e m a i n f a c t o r w h i c h m a k e s t h e a n t e r o - p o s t e r a o r electrodes less efficient t h a n the m e d l o lateral electrodes in s u p p o r t i n g lateral h y p o t h a l a m l c a n d v e n t r a l t e g m e n t a l s e l f - s t i m u l a t i o n Thus, t h e possible differences e i t h e r in t h e t h r e s h o l d to ehclt direct discharges or in the n u m b e r of t h e excited r e w a r d i n g e l e m e n t s [3] can only be a d d i t i o n a l , b u t s u b o r d i n a t e , variables The neural elem e n t s t r a n s m i t t i n g r e w a r d i n g e x c i t e m e n t seem, t h e r e f o r e to b e aligned, or e l o n g a t e d , in t h e sagittal axis of t h e brain, similar to t h e lateral h y p o t h a l a m i c r e v e r b e r a t o r y l o o p s of the neural p a t h w a y of t h e medial f o r e b r a l n b u n d l e .

REFERENCES 1 2 3

MlUhouse, O. E. A Golgl study of the descending medial forebrain bundle. Brim Res 15: 3 4 1 - 3 6 3 , 1969_ Szabo, I. Path neuron system of medial forebram bundle as a possible substrate for hypothalamlc self-snmulatlon Phystol Behav 1 0 : 3 1 5 - 3 2 8 , 1 9 7 3 Szabo, I. and P M. Mllner. Self-stimulation m rats tip alignment influences the effectweness of bipolar electrodes Brim Res 48: 2 4 3 - 2 5 0 , 1972

4. Szabo, 1 , E Nad and C Szabo Pole reversals and hypothalamlc self-stimulation ascending spread of rewarding e-,mtatlon Phystol Behav 9: 147-150, 1972 5 Szabo, I., E. Rozkowska and P Kolta Influence of contingent amygdalold stimulation on lateral hypothalamlc-medlal forebrain bundle self-stimulation Phystol Behav 9: 8 3 9 - 8 4 9 , 1972